Background: Although maternal mortality is declining in most countries, it remains a significant public health problem worldwide, with high rates, particularly in developing and insecure countries like ours. Objective...Background: Although maternal mortality is declining in most countries, it remains a significant public health problem worldwide, with high rates, particularly in developing and insecure countries like ours. Objective: To study the epidemiological factors and factors associated with the occurrence of maternal death in the Gynecology-Obstetrics Department of University Hospital of Tengandogo. Method: It was a retrospective case-control study with a descriptive and analytical purpose over a period of 6 years from January 1, 2017 to December 31, 2022. Cases were women with maternal deaths during the study period. Data processing and analysis were performed using Stata version 13 software. Univariate and multivariate analyses were performed with Stata version 13 software, and logistic regression modeling was used to estimate crude and adjusted odds ratios (OR), their 95% confidence intervals (CI), and the threshold for statistical significance was set at a p value < 0.05. Results: A total of 372 patients were included in the study, including 146 cases of maternal death. The in-hospital maternal mortality rate was 1933 deaths per 100,000 live births. The average age was 28.5 years. 58.9% of patients lived in rural areas. Married patients accounted for 88.7% of cases. The average parity was 3. Direct obstetrical causes were the main causes of death, accounting for 72.6%. They were dominated by post-partum hemorrhage (24.2%), puerperal infection (18.6%), pre-eclampsia/eclampsia (16.1%) and retroplacental hematoma (8.9%). Chronic anemia (12.9%) was the main indirect obstetric cause. Risk factors associated with maternal death were primiparity (OR for paucigravida and multigravida at 0.05;P = 0.001);ambulance transport (OR for patients referred and brought in by personal vehicle = 0.3, p < 0.001) and vaginal delivery (OR for cesarean deliveries = 0.4, p < 0.001). Conclusion: To reduce maternal mortality in Burkina Faso, strategies such as educating women about danger signs during pregnancy and promoting women’s education can be adopted.展开更多
Objective: To determine the prevalence, level of severity of potential drug–drug interactions(PDDIs) and the associated factors for PDDIs in hospitalized pediatric patients of Gondar University Hospital.Methods: A re...Objective: To determine the prevalence, level of severity of potential drug–drug interactions(PDDIs) and the associated factors for PDDIs in hospitalized pediatric patients of Gondar University Hospital.Methods: A retrospective cross-sectional study was conducted for a period of 3 months from March to May 2014 in pediatric wards of Gondar University Hospital. Systematic random sampling technique was used to select charts from all pediatric patients' charts with every 7th interval to get sample size of 384. Univariate and multivariate analysis were performed to compute crude odds ratio and adjusted odds ratio respectively. Statistical significance was set at P value < 0.05.Results: A total of 176(45.8%) patients had at least one PDDI. A total of 393 PDDIs,which were comprised of 283 types of interacting combinations, were identified. Of the total of 393 PDDIs, most were of moderate severity [201(51%)] followed by minor [152(39%)] and major severity [40(10%)]. The most common interacting pairs of major severity were gentamicin + furosemide(6), cotrimoxazole + methotrexate(4) and phenytoin + artemether(4). The occurrence of PDDIs was significantly associated with age and polypharmacy.Conclusions: The study showed that most of the interactions had moderate severity followed by minor severity. Age and polypharmacy were found to show statistically significant association with the occurrence of PDDIs. Due to sensitive nature of pediatrics population, close monitoring is recommended for the detection and management of PDDIs to prevent its negative consequences.展开更多
The object of this study is to assess the Ivlg （intravenous immunoglobulin） use in inflammatory systemic and immune-mediated illnesses, in patients older than 18 years in a tertiary hospital. The assessment also int...The object of this study is to assess the Ivlg （intravenous immunoglobulin） use in inflammatory systemic and immune-mediated illnesses, in patients older than 18 years in a tertiary hospital. The assessment also intends to ensure if the clinical indications matched with the evidence-based clinical guidelines recommendations of use. Analytical, observational, transversal and retrospective study carried out during 2012. Patients with inflammatory systemic and immuno-mediated illnesses, older than 18 years old, were included. The data collected were： age, sex, number of administrations, dosage, frequency, commercial brand and the indication for what the Ivlg treatment has been prescribed. As a reference guide the British Health Department Clinical Guidelines for Immunoglobulin Use （2nd edition, 2008, and 2nd edition update 2011） and its Spanish adaption were used. The lvlg treatment was justified by a grade of recommendation A, B or C in 41% of the indications. Thus in 59% （grey indications or unclear diagnosis） the IvIg use would be questionable because of its weak evidence. It was found one indication for what the prescription of IvIg was clearly not recommended. The inflammatory systemic and immune-mediated diseases include many pathologies for what the IvIg use has not been properly studied. There is a need of consensus guidelines for IvIg use to guide doctors and pharmacists in their clinical practice. Moreover, it is important to prioritize which indications and circumstances are of first importance to have their supply guaranteed.展开更多
<span style="font-family:Verdana;">Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related dea...<span style="font-family:Verdana;">Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.</span>展开更多
Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this procedure.This meta-analysis aim...Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this procedure.This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.Methods:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational status.Hazard ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined.The search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,2022.Meta-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were excluded.The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.Results:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.Conclusion:RAS,BRAF,and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer.No conclusion can be drawn for PIK3CA due to the limited literature availability.These data support the integration of RAS,BRAF,and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis.Nevertheless,we have to consider several limitations,the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival(DFS)or RFS;the inclusion of patients with minimal residual disease and unconsidered potential confounding factors,such as variability in resectability definitions,chemotherapy use,and a potential interaction between biological markers and pre-and post-resection pharmacological treatments.展开更多
Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase...Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.展开更多
Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, ...Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.展开更多
Feasibility of endoscopic retrograde cholangiopancreatography(ERCP) for biliary drainage is not always applicable due to anatomical alterations or to inability to access the papilla. Percutaneous transhepatic biliary ...Feasibility of endoscopic retrograde cholangiopancreatography(ERCP) for biliary drainage is not always applicable due to anatomical alterations or to inability to access the papilla. Percutaneous transhepatic biliary drainage has always been considered the only alternative for this indication. However,endoscopic ultrasonography-guided biliary drainage represents a valid option to replace percutaneous transhepatic biliary drainage when ERCP fails. According to the access site to the biliary tree,two kinds of approaches may be described: the intrahepatic and the extrahepatic. Endoscopic ultrasonography-guided rendezvous transpapillary drainage is performed where the second portion of the duodenum is easily reached but conventional ERCP fails. The recent introduction of self-expandable metal stents and lumen-apposing metal stents has improved this field. However,the role of the latter is still controversial. Echoendoscopic transmural biliary drainage can be challenging with potential severe adverse events. Therefore,trained endoscopists,in both ERCP and endoscopic ultrasonography are needed with surgical and radiological backup.展开更多
Objective: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus(PDA) in premature neonates with significant clinical and hemodynamic repercussions(C...Objective: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus(PDA) in premature neonates with significant clinical and hemodynamic repercussions(CHRs) and to determine the effect of these respective treatments on renal function.Methods: A retrospective study of cases of PDA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin[0.2 mg/(kg$d), 3-day cycle], ibuprofen [10 mg/(kg$d) followed by 5 mg/(kg$d), 3-day cycle], and paracetamol(15 mg/kg every 6 h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age,newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels(sodium and potassium).Results: Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5 d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of9.66 d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ductus.Conclusions: Oral indomethacin was effective for closure of the PDA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in premature neonates with severe CHRs and contraindications for indomethacin was ineffective.However, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.展开更多
Dietary fiber is a non-digestible carbohydrate providing beneficial effects for bowel health. The aim of this study was to evaluate the clinical effects of fiber supplementation in enteral feeding on elderly patients ...Dietary fiber is a non-digestible carbohydrate providing beneficial effects for bowel health. The aim of this study was to evaluate the clinical effects of fiber supplementation in enteral feeding on elderly patients suffering from diarrhea. This study was conducted in 15 patients (7 men and 8 women, 79.0 ± 7.5 years) who had loose stools or diarrhea during enteral nutrition. The enteral formula was supplemented with soluble dietary fiber (5.2 g/day) for 3 weeks, which was then discontinued for 1 week to confirm its effects. The effects of soluble dietary fiber on stool frequency, the Bristol Stool Form Scale (which is designed to measure stool consistency), plasma diamine oxidase (DAO) activity, and concentrations of plasma short-chain fatty acids (SCFA) were evaluated. After supplementation with soluble dietary fiber, there were no significant differences in stool frequency but there was a significant improvement in stool consistency (P < 0.05). Furthermore, ingestion of soluble dietary fiber resulted in increased plasma DAO activity and significantly increased levels of plasma SCFA (P < 0.05). Supplementation with soluble dietary fiber may be beneficial for improving stool consistency in patients suffering from diarrhea during enteral nutrition. A further controlled trial is warranted to examine the preventive effects of soluble dietary fiber in patients suffering from diarrhea.展开更多
It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The a...It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.展开更多
Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpo...Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpose, 1000 μg intrarectal (insertion of five 200 μg tablets) has been recommended as the third line after injectable oxytocin and methylergometrine. We proposed to manufacture a 1000 μg misoprostol suppository by determining formulation, release and stability. The administration facility was also evaluated. Several formulations of misoprostol suppositories were set up and evaluated. Misoprostol tablets and lipophilic bases (Hard fat—Adeps solidus Ph. Eur., Witepsol? H15 and Suppocire? AM and AS2X) were used to obtain suppositories. Surfactants were also tested (polysorbates Tween? 20, Tween? 80 and sodium lauryl sulfate (SLS)). The formula was monitored by the misoprostol release curve with an in vitro test and dosed by a HPLC method. Stability was determined by evaluating the percentage of misoprostol content remaining over the time in suppositories stored at 4℃ and 25℃. Facility of use versus tablets was evaluated by obstetricians of a Swiss regional hospital using a questionnaire. Misoprostol release was facilitated by adding surfactant to the lipophilic base. After 30 minutes, 59% ± 1.4% and 57% ± 8.2% of misoprostol was released with Adeps solidus + 1% SLS and Adeps solidus + 5% Tween 20 respectively. SLS was discarded to the final formula because of its irritating effect. After 7 months, suppositories still contained 94% ± 3.7% misoprostol with storage at 4℃. The administration was considered easier and faster compared with intra rectal use of tablets. The formula, consisting of 5 crushed misoprostol tablets dispersed in a suppository base made of Adeps solidus + 5% Tween? 20, is stable for at least 7 months at 4?C and facilitates the rectal administration of misoprostol in the treatment of PPH.展开更多
BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received stric...BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin.The dose of warfarin was increased to 350%in 3 mo before reaching the lower international normalized ratio treatment window.No obvious adverse reaction occurred during the drugadjustment period.This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range.CONCLUSION Anticoagulation for valve replacement in Chinese patients differs from that in other races.Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.展开更多
The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments...The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intravenously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7%-109.4%and<10%,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 μg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclusion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed.展开更多
Objectives: To classify community pharmacies (CPs) in Riyadh, Saudi Arabia, in terms of the quality of medicines sold by them, using?the lot quality assurance sampling (LQAS) technique with a predefined threshold. Met...Objectives: To classify community pharmacies (CPs) in Riyadh, Saudi Arabia, in terms of the quality of medicines sold by them, using?the lot quality assurance sampling (LQAS) technique with a predefined threshold. Methods: Riyadh CPs were divided into 2 categories (“lots” for the purpose of LQAS), i.e., chain and independent CPs. Upper and lower rate thresholds for CPs that sell low-quality medicines were predefined as 20% and 5%, respectively. Consumer and provider risks were predefined as 0.05 and 0.10, respectively. The calculated number of randomly selected CPs required in each lot was 36;then, sale of low-quality medicines in >3 CPs implies a prevalence of >20% of such CPs according to LQAS. A randomly selected brand of amoxicillin (selected as a quality indicator of medicines because it is both widely counterfeited and heat-sensitive) was purchased from each pharmacy by a “mystery shopper”, checked for authenticity, and analyzed for drug content and content uniformity using a validated HPLC method. Results: Substandard amoxicillin was purchased in 9 pharmacies (4 chains and 5 independent). Both lots were thus rejected as unacceptable, which may indicate that consumers in Riyadh are at risk of purchasing substandard medicines at CPs. Conclusions: The quality of medicines sold in CPs in Riyadh did not meet our acceptability criterion, and appropriate intervention by decision makers is recommended. LQAS proved to be a practical, economical, and statistically valid sampling method for surveying the quality of medicines. It should enable decision makers to allocate resources for improvement more efficiently.展开更多
Contents1.Introduction2.Methods2.1 Guideline project group2.2 Registration and methodology2.3 Guideline process2.3.1 Formulation of clinical questions2.3.2 Systematic literature review2.3.3 Consensus on recommendation...Contents1.Introduction2.Methods2.1 Guideline project group2.2 Registration and methodology2.3 Guideline process2.3.1 Formulation of clinical questions2.3.2 Systematic literature review2.3.3 Consensus on recommendations3.Recommendations3.1 General principles3.2 Drug delivery,reception and storage3.3 Dispensing of antineoplastics3.4 Administration and carrying of antineoplastics3.5 Prevention measures for blood,excreta(urine and feces),and vomitus of patients3.6 Medical waste disposal4.Discussion5.Conclusions 1.Introduction The exposure of nurses,pharmacists,physicians,laboratory technicians,drug transportationstaff,,patients and caregivers in medical institutions to antineoplastics is a potential health hazard.Furthermore,these antineoplastics are potential contaminants if disposed inappropriately to the environment,thus making it an issue of immense concern in medical safety.A drug is declared hazardous if it shows one or more of the following six impacts on humans or animals:carcinogenicity,teratogenicity or other developmental toxicity,reproductive toxicity,organ toxicity at low doses,and genotoxicity.Hazardous drugs also include new drugs possessing structural and toxicity profiles similar to the existing hazardous drugs(1).展开更多
Background: To explore the effects of cholestasis on whole blood concentration of tacrolimus (TAC), an immunosup-pressant, we investigated the relationship among blood TAC concentration, bile flow, and TAC metabolites...Background: To explore the effects of cholestasis on whole blood concentration of tacrolimus (TAC), an immunosup-pressant, we investigated the relationship among blood TAC concentration, bile flow, and TAC metabolites in bile, as well as the relationship between total bilirubin (T-Bil), an index of cholestasis, and blood TAC concentration, in liver transplant recipients. Methods: Data were collected retrospectively from 16 male and 19 female patients (mean age: 38 years;range: 12 -59 years) who had undergone a living-related liver transplantation at Kyoto Prefectural University of Medicine from 2004 through 2008. Analysis of TAC, demethyl-TAC, and hydroxy-TAC in bile was performed by LC-MS/MS. Results: There was no correlation between the ratio of TAC metabolite to TAC in bile (M/P) of demethyl-TAC and post operation days (POD), whereas a weak linear correlation was demonstrated between M/P of hydroxy-TAC and POD (r = -0.345). Moreover, linear correlations were not observed between M/P and the TAC trough level normalized dose (TLTAC/dose), and between TLTAC/dose and POD. A negative linear correlation was demonstrated between bile flow and T-Bil in blood (r = -0.495). Furthermore, a positive linear correlation was observed between TLTAC/dose and T-Bil (r = 0.598), whereas there was no correlation between bile flow and TLTAC/dose. Conclusions: Improvement of hepatic function and the increase of TAC clearance after postoperative day 7 did not significantly contribute to hepatic TAC metabolism, bile excretion, and TLTAC/dose. Postoperative biliary stricture from liver transplantation with/without biliary drainage caused inter-and intra-patient variability in TLTAC/dose after liver transplantation, which could be assessed by T-Bil. T-Bil in blood might be a predictive biomarker for determining the degree of bile duct stricture and TAC dose in liver transplantation patients. Along with an appropriate dosing regimen, therapeutic drug monitoring including T-Bil would be beneficial and enable individual adjustment of TAC dose in liver transplantation patients.展开更多
文摘Background: Although maternal mortality is declining in most countries, it remains a significant public health problem worldwide, with high rates, particularly in developing and insecure countries like ours. Objective: To study the epidemiological factors and factors associated with the occurrence of maternal death in the Gynecology-Obstetrics Department of University Hospital of Tengandogo. Method: It was a retrospective case-control study with a descriptive and analytical purpose over a period of 6 years from January 1, 2017 to December 31, 2022. Cases were women with maternal deaths during the study period. Data processing and analysis were performed using Stata version 13 software. Univariate and multivariate analyses were performed with Stata version 13 software, and logistic regression modeling was used to estimate crude and adjusted odds ratios (OR), their 95% confidence intervals (CI), and the threshold for statistical significance was set at a p value < 0.05. Results: A total of 372 patients were included in the study, including 146 cases of maternal death. The in-hospital maternal mortality rate was 1933 deaths per 100,000 live births. The average age was 28.5 years. 58.9% of patients lived in rural areas. Married patients accounted for 88.7% of cases. The average parity was 3. Direct obstetrical causes were the main causes of death, accounting for 72.6%. They were dominated by post-partum hemorrhage (24.2%), puerperal infection (18.6%), pre-eclampsia/eclampsia (16.1%) and retroplacental hematoma (8.9%). Chronic anemia (12.9%) was the main indirect obstetric cause. Risk factors associated with maternal death were primiparity (OR for paucigravida and multigravida at 0.05;P = 0.001);ambulance transport (OR for patients referred and brought in by personal vehicle = 0.3, p < 0.001) and vaginal delivery (OR for cesarean deliveries = 0.4, p < 0.001). Conclusion: To reduce maternal mortality in Burkina Faso, strategies such as educating women about danger signs during pregnancy and promoting women’s education can be adopted.
基金Supported by University of Gondar(Grant No.Uo G/Re/Core/Pro/138862/2014)
文摘Objective: To determine the prevalence, level of severity of potential drug–drug interactions(PDDIs) and the associated factors for PDDIs in hospitalized pediatric patients of Gondar University Hospital.Methods: A retrospective cross-sectional study was conducted for a period of 3 months from March to May 2014 in pediatric wards of Gondar University Hospital. Systematic random sampling technique was used to select charts from all pediatric patients' charts with every 7th interval to get sample size of 384. Univariate and multivariate analysis were performed to compute crude odds ratio and adjusted odds ratio respectively. Statistical significance was set at P value < 0.05.Results: A total of 176(45.8%) patients had at least one PDDI. A total of 393 PDDIs,which were comprised of 283 types of interacting combinations, were identified. Of the total of 393 PDDIs, most were of moderate severity [201(51%)] followed by minor [152(39%)] and major severity [40(10%)]. The most common interacting pairs of major severity were gentamicin + furosemide(6), cotrimoxazole + methotrexate(4) and phenytoin + artemether(4). The occurrence of PDDIs was significantly associated with age and polypharmacy.Conclusions: The study showed that most of the interactions had moderate severity followed by minor severity. Age and polypharmacy were found to show statistically significant association with the occurrence of PDDIs. Due to sensitive nature of pediatrics population, close monitoring is recommended for the detection and management of PDDIs to prevent its negative consequences.
文摘The object of this study is to assess the Ivlg （intravenous immunoglobulin） use in inflammatory systemic and immune-mediated illnesses, in patients older than 18 years in a tertiary hospital. The assessment also intends to ensure if the clinical indications matched with the evidence-based clinical guidelines recommendations of use. Analytical, observational, transversal and retrospective study carried out during 2012. Patients with inflammatory systemic and immuno-mediated illnesses, older than 18 years old, were included. The data collected were： age, sex, number of administrations, dosage, frequency, commercial brand and the indication for what the Ivlg treatment has been prescribed. As a reference guide the British Health Department Clinical Guidelines for Immunoglobulin Use （2nd edition, 2008, and 2nd edition update 2011） and its Spanish adaption were used. The lvlg treatment was justified by a grade of recommendation A, B or C in 41% of the indications. Thus in 59% （grey indications or unclear diagnosis） the IvIg use would be questionable because of its weak evidence. It was found one indication for what the prescription of IvIg was clearly not recommended. The inflammatory systemic and immune-mediated diseases include many pathologies for what the IvIg use has not been properly studied. There is a need of consensus guidelines for IvIg use to guide doctors and pharmacists in their clinical practice. Moreover, it is important to prioritize which indications and circumstances are of first importance to have their supply guaranteed.
文摘<span style="font-family:Verdana;">Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.</span>
基金partially funded by Italian Ministry of Health—Ricerca Corrente(no grant number).
文摘Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this procedure.This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.Methods:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational status.Hazard ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined.The search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,2022.Meta-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were excluded.The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.Results:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.Conclusion:RAS,BRAF,and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer.No conclusion can be drawn for PIK3CA due to the limited literature availability.These data support the integration of RAS,BRAF,and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis.Nevertheless,we have to consider several limitations,the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival(DFS)or RFS;the inclusion of patients with minimal residual disease and unconsidered potential confounding factors,such as variability in resectability definitions,chemotherapy use,and a potential interaction between biological markers and pre-and post-resection pharmacological treatments.
基金supported in part by grants from the Young Scientists Awards Foundation of Shandong Province of China,No.BS2013YY049the China Postdoctoral Science Foundation,No.2012M511036
文摘Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.
文摘Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.
文摘Feasibility of endoscopic retrograde cholangiopancreatography(ERCP) for biliary drainage is not always applicable due to anatomical alterations or to inability to access the papilla. Percutaneous transhepatic biliary drainage has always been considered the only alternative for this indication. However,endoscopic ultrasonography-guided biliary drainage represents a valid option to replace percutaneous transhepatic biliary drainage when ERCP fails. According to the access site to the biliary tree,two kinds of approaches may be described: the intrahepatic and the extrahepatic. Endoscopic ultrasonography-guided rendezvous transpapillary drainage is performed where the second portion of the duodenum is easily reached but conventional ERCP fails. The recent introduction of self-expandable metal stents and lumen-apposing metal stents has improved this field. However,the role of the latter is still controversial. Echoendoscopic transmural biliary drainage can be challenging with potential severe adverse events. Therefore,trained endoscopists,in both ERCP and endoscopic ultrasonography are needed with surgical and radiological backup.
文摘Objective: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus(PDA) in premature neonates with significant clinical and hemodynamic repercussions(CHRs) and to determine the effect of these respective treatments on renal function.Methods: A retrospective study of cases of PDA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin[0.2 mg/(kg$d), 3-day cycle], ibuprofen [10 mg/(kg$d) followed by 5 mg/(kg$d), 3-day cycle], and paracetamol(15 mg/kg every 6 h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age,newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels(sodium and potassium).Results: Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5 d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of9.66 d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ductus.Conclusions: Oral indomethacin was effective for closure of the PDA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in premature neonates with severe CHRs and contraindications for indomethacin was ineffective.However, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.
文摘Dietary fiber is a non-digestible carbohydrate providing beneficial effects for bowel health. The aim of this study was to evaluate the clinical effects of fiber supplementation in enteral feeding on elderly patients suffering from diarrhea. This study was conducted in 15 patients (7 men and 8 women, 79.0 ± 7.5 years) who had loose stools or diarrhea during enteral nutrition. The enteral formula was supplemented with soluble dietary fiber (5.2 g/day) for 3 weeks, which was then discontinued for 1 week to confirm its effects. The effects of soluble dietary fiber on stool frequency, the Bristol Stool Form Scale (which is designed to measure stool consistency), plasma diamine oxidase (DAO) activity, and concentrations of plasma short-chain fatty acids (SCFA) were evaluated. After supplementation with soluble dietary fiber, there were no significant differences in stool frequency but there was a significant improvement in stool consistency (P < 0.05). Furthermore, ingestion of soluble dietary fiber resulted in increased plasma DAO activity and significantly increased levels of plasma SCFA (P < 0.05). Supplementation with soluble dietary fiber may be beneficial for improving stool consistency in patients suffering from diarrhea during enteral nutrition. A further controlled trial is warranted to examine the preventive effects of soluble dietary fiber in patients suffering from diarrhea.
文摘It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
文摘Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpose, 1000 μg intrarectal (insertion of five 200 μg tablets) has been recommended as the third line after injectable oxytocin and methylergometrine. We proposed to manufacture a 1000 μg misoprostol suppository by determining formulation, release and stability. The administration facility was also evaluated. Several formulations of misoprostol suppositories were set up and evaluated. Misoprostol tablets and lipophilic bases (Hard fat—Adeps solidus Ph. Eur., Witepsol? H15 and Suppocire? AM and AS2X) were used to obtain suppositories. Surfactants were also tested (polysorbates Tween? 20, Tween? 80 and sodium lauryl sulfate (SLS)). The formula was monitored by the misoprostol release curve with an in vitro test and dosed by a HPLC method. Stability was determined by evaluating the percentage of misoprostol content remaining over the time in suppositories stored at 4℃ and 25℃. Facility of use versus tablets was evaluated by obstetricians of a Swiss regional hospital using a questionnaire. Misoprostol release was facilitated by adding surfactant to the lipophilic base. After 30 minutes, 59% ± 1.4% and 57% ± 8.2% of misoprostol was released with Adeps solidus + 1% SLS and Adeps solidus + 5% Tween 20 respectively. SLS was discarded to the final formula because of its irritating effect. After 7 months, suppositories still contained 94% ± 3.7% misoprostol with storage at 4℃. The administration was considered easier and faster compared with intra rectal use of tablets. The formula, consisting of 5 crushed misoprostol tablets dispersed in a suppository base made of Adeps solidus + 5% Tween? 20, is stable for at least 7 months at 4?C and facilitates the rectal administration of misoprostol in the treatment of PPH.
文摘BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin.The dose of warfarin was increased to 350%in 3 mo before reaching the lower international normalized ratio treatment window.No obvious adverse reaction occurred during the drugadjustment period.This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range.CONCLUSION Anticoagulation for valve replacement in Chinese patients differs from that in other races.Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.
基金supported by the Japan Society for the Promotion of Science KAKENHI(Grant No.:JP19H00349).
文摘The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intravenously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7%-109.4%and<10%,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 μg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclusion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed.
文摘Objectives: To classify community pharmacies (CPs) in Riyadh, Saudi Arabia, in terms of the quality of medicines sold by them, using?the lot quality assurance sampling (LQAS) technique with a predefined threshold. Methods: Riyadh CPs were divided into 2 categories (“lots” for the purpose of LQAS), i.e., chain and independent CPs. Upper and lower rate thresholds for CPs that sell low-quality medicines were predefined as 20% and 5%, respectively. Consumer and provider risks were predefined as 0.05 and 0.10, respectively. The calculated number of randomly selected CPs required in each lot was 36;then, sale of low-quality medicines in >3 CPs implies a prevalence of >20% of such CPs according to LQAS. A randomly selected brand of amoxicillin (selected as a quality indicator of medicines because it is both widely counterfeited and heat-sensitive) was purchased from each pharmacy by a “mystery shopper”, checked for authenticity, and analyzed for drug content and content uniformity using a validated HPLC method. Results: Substandard amoxicillin was purchased in 9 pharmacies (4 chains and 5 independent). Both lots were thus rejected as unacceptable, which may indicate that consumers in Riyadh are at risk of purchasing substandard medicines at CPs. Conclusions: The quality of medicines sold in CPs in Riyadh did not meet our acceptability criterion, and appropriate intervention by decision makers is recommended. LQAS proved to be a practical, economical, and statistically valid sampling method for surveying the quality of medicines. It should enable decision makers to allocate resources for improvement more efficiently.
文摘Contents1.Introduction2.Methods2.1 Guideline project group2.2 Registration and methodology2.3 Guideline process2.3.1 Formulation of clinical questions2.3.2 Systematic literature review2.3.3 Consensus on recommendations3.Recommendations3.1 General principles3.2 Drug delivery,reception and storage3.3 Dispensing of antineoplastics3.4 Administration and carrying of antineoplastics3.5 Prevention measures for blood,excreta(urine and feces),and vomitus of patients3.6 Medical waste disposal4.Discussion5.Conclusions 1.Introduction The exposure of nurses,pharmacists,physicians,laboratory technicians,drug transportationstaff,,patients and caregivers in medical institutions to antineoplastics is a potential health hazard.Furthermore,these antineoplastics are potential contaminants if disposed inappropriately to the environment,thus making it an issue of immense concern in medical safety.A drug is declared hazardous if it shows one or more of the following six impacts on humans or animals:carcinogenicity,teratogenicity or other developmental toxicity,reproductive toxicity,organ toxicity at low doses,and genotoxicity.Hazardous drugs also include new drugs possessing structural and toxicity profiles similar to the existing hazardous drugs(1).
文摘Background: To explore the effects of cholestasis on whole blood concentration of tacrolimus (TAC), an immunosup-pressant, we investigated the relationship among blood TAC concentration, bile flow, and TAC metabolites in bile, as well as the relationship between total bilirubin (T-Bil), an index of cholestasis, and blood TAC concentration, in liver transplant recipients. Methods: Data were collected retrospectively from 16 male and 19 female patients (mean age: 38 years;range: 12 -59 years) who had undergone a living-related liver transplantation at Kyoto Prefectural University of Medicine from 2004 through 2008. Analysis of TAC, demethyl-TAC, and hydroxy-TAC in bile was performed by LC-MS/MS. Results: There was no correlation between the ratio of TAC metabolite to TAC in bile (M/P) of demethyl-TAC and post operation days (POD), whereas a weak linear correlation was demonstrated between M/P of hydroxy-TAC and POD (r = -0.345). Moreover, linear correlations were not observed between M/P and the TAC trough level normalized dose (TLTAC/dose), and between TLTAC/dose and POD. A negative linear correlation was demonstrated between bile flow and T-Bil in blood (r = -0.495). Furthermore, a positive linear correlation was observed between TLTAC/dose and T-Bil (r = 0.598), whereas there was no correlation between bile flow and TLTAC/dose. Conclusions: Improvement of hepatic function and the increase of TAC clearance after postoperative day 7 did not significantly contribute to hepatic TAC metabolism, bile excretion, and TLTAC/dose. Postoperative biliary stricture from liver transplantation with/without biliary drainage caused inter-and intra-patient variability in TLTAC/dose after liver transplantation, which could be assessed by T-Bil. T-Bil in blood might be a predictive biomarker for determining the degree of bile duct stricture and TAC dose in liver transplantation patients. Along with an appropriate dosing regimen, therapeutic drug monitoring including T-Bil would be beneficial and enable individual adjustment of TAC dose in liver transplantation patients.
