While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effecti...While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.展开更多
Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of ...Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.展开更多
In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary m...In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary modes of treatment. CurCousin<sup>®</sup> is a nutritional ingredient containing bioactive Calebin A, (analog of Curcumin) with self-affirmed GRAS status. CurCousin<sup>®</sup> has been a clinically studied dietary supplement ingredient with a positive impact on body weight, lipid levels and metabolic health. Bioenhancers play an important role in increasing the bioavailability of the active in turn enhancing efficacy as well as reducing the dosage required to achieve the therapeutic effect. This study investigated the possible pharmacokinetic interaction between CurCousin<sup>®</sup> at two different doses (2.25 and 4.5 mg/kg) in the presence and absence of BioPerine<sup>®</sup> (0.27 mg/kg), a natural bioenhancer in Sprague-Dawley rats. The results revealed that the addition of BioPerine<sup>®</sup> into CurCousin<sup>®</sup> (2.25 mg/kg) half the dose when administered enhances the bioavailability and was equipotent to CurCousin<sup>®</sup> (4.5 mg/kg) double the dose without BioPerine<sup>®</sup>. Thus, leading to future clinical studies to evaluate its improved pharmacological efficacy as well as reduced therapeutic dosage.展开更多
Aim To investigate whether modified-release cefaclor capsules could lead to a more suitable pharmacokinetic profile in the plasma. Methods Cefaclor pellets were prepared by extrusion/spheronization and coated by Eudra...Aim To investigate whether modified-release cefaclor capsules could lead to a more suitable pharmacokinetic profile in the plasma. Methods Cefaclor pellets were prepared by extrusion/spheronization and coated by Eudragit L30D-55 or Eudragit NE30D, then the two sorts of pellets were filled to capsules in a 35：65 ratio to made a modified-release （MR） capsules. The bioavailability of the MR capsules was studied in 24 healthy volunteers after oral administration in a fast state using a commercially available immediate release （IR） capsule as a reference. Results The results showed that the MR formulation had a relatively good bioavailability compared with the commercial capsules, as well as a longer time keeping drug level above MIC than immediate release capsule. The relative bioavailability of the MR capsules was 97.4- 12.1%. Conclusion The data of the present study indicate that time of cefaclor plasma concentration above MIC can be substantially prolonged if cefaclor is administered as a modified- release product.展开更多
A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined ...A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined by mass detector. The calibration curve of loratadine was linear within the range of 0.4～100 ng·mL -1 with r=0.9995 . The recovery of this method was within 95%～104%, within day and between day RSD were less than 12%. To study the pharmacokinetics and relative bioavailability of loratadine tablets, two formulations of loratadine tablets were given to 18 healthy male volunteers according to a randomized 2 way cross over design. The C max , AUC 0 t and T max values of the two formulations were 51.89±20.18 ng·mL -1 and 52.48±22.35 ng·mL -1 ; 140.75±88.42 ng·h·mL -1 and 147.24±92.33 ng·h·mL -1 ; 0.81±0.35 h and 0.81±0.27 h respectively. Results from statistic analysis showed that there were no significant difference between the C max , AUC 0-t and T max values of the two formulations. The relative bioavailability of tablets I with respect to tablets II was 97%±13% from the AUC 0 t measurement. Bioequivalance was observed between the two tablets.展开更多
The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma con...The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.展开更多
A new pre-column derivation HPLC method with solid-phase extraction to determine captopril in human plasma was established. Derivation products were extracted by a solid-phase extraction method after the reagent, p-a-...A new pre-column derivation HPLC method with solid-phase extraction to determine captopril in human plasma was established. Derivation products were extracted by a solid-phase extraction method after the reagent, p-a-dibromoacetophenone(p-BPB), was added in the plasma samples. The samples were analyzed in a VP-ODS column with UV-detector. The calibration curve of captopril was linear within the range of 5~1000 ngmL-1 with r=0.9987, the recovery of this method was 98.652.04%, within day and between day RSD were no more than 3.4% and 8.4% respectively. To study the pharmacokinetics and the relative bioavailability of captopril tablets, two formulations of captopril tablets were given to 18 healthy male volunteers according to a randomized 2-way cross-over design with a 1-week washout period. The respective AUC0~6 , Cmax and Tmax values of the two formulations were 424.5125.7 and 439.4113.3 mghL-1; 505.9244.6 and 504.8172.2 mgL-1; 0.6620.181 and 0.5280.176 h. Results from statistics analysis showed that there were no significant difference between the AUC0~6 , Cmax and Tmax values of the two formulations, The relative bioavailability of tablets I with respect to II was 96.114.6% from AUC0~6 measurement. Bioequivalance was observed between the two tablets.展开更多
Aim To establish a sensitive and specific liquid chromatography-mass spectrometry (HPLC-MS) method for measuring lovastatin level in human plasma and the relative bioavailability. Methods Lovastatin in the plasma was ...Aim To establish a sensitive and specific liquid chromatography-mass spectrometry (HPLC-MS) method for measuring lovastatin level in human plasma and the relative bioavailability. Methods Lovastatin in the plasma was extracted with acetoacetate. Simvastatin was added as internal standard (IS). Samples were separated on a C_ 18 column with a mobile phase consisting of methanol and 50 mmol·L~ -1 sodium acetate (88 ∶ 12). The flow rate was 1 mL·min~ -1 . Sample was detected using an electrospray ionization (ES...展开更多
The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assay...The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.展开更多
The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curc...The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curcumin,a polyphenolic compound derived from turmeric,exhibits diverse pharmacological properties,including anti-inflammatory,antioxidant,and anticancer effects.Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms.This review examines the current literature on the interactions between curcumin and the gut microbiome.A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance.Key findings from studies exploring curcumin's efficacy in neurological disorders,gastrointestinal diseases,and metabolic dysfunction are synthesized and discussed.Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function,leading to beneficial effects on gut health and homeostasis.Mechanisms underlying curcumin's therapeutic effects include immune modulation,neuroprotection,and inflammation regulation.However,challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome.The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions.Further research is needed to optimize curcumin formulations,improve bioavailability,and address safety concerns.展开更多
The aim of this study was to determine the apparent （AME） ＆ true （TMEn） metabolizable energy as well as the crude protein （CP） ＆ amino acid （AA） total tract （by excreta collection） digestibility （bioavail...The aim of this study was to determine the apparent （AME） ＆ true （TMEn） metabolizable energy as well as the crude protein （CP） ＆ amino acid （AA） total tract （by excreta collection） digestibility （bioavailability） of field pea seeds （FPS） of the Greek cultivar ＂Olympos＂. Forty eight broilers were placed in individual cages and randomly allocated into 4 dietary treatments. Birds consumed 80 g/d of either a typical commercial diet or the same diet in which 100, 200 or 300 g/kg had been substituted by ground FPS. The experiment lasted 15 d. Apparent and true CP bioavailability of FPS were significantly decreased （P 〈 0.05） only at the inclusion rate of 300 g/kg. AA bioavailability remained at high levels （-0.80）, with the exception of methionine and valine and was similar to CP mean. The mean AME and TMEn values of FPS were estimated equal to 10.8 and 11.0 MJ ME/kg, respectively.展开更多
The relative bioavailability of famotidine sustained release (SR) tablets was studied in 16 healthy male volunteers. Famotidine plasma concentration was determined by HPLC method, and the plasma concentration time d...The relative bioavailability of famotidine sustained release (SR) tablets was studied in 16 healthy male volunteers. Famotidine plasma concentration was determined by HPLC method, and the plasma concentration time data were processed with the method provided by USP XXIII. For single dose administration the peak plasma concentration occurring at 8 13±0 34 h was 69 52±3 00 ng/ml and the relative bioavailability was 112 4±8 6%. For multiple dose administration the peak plasma concentration of SR tablet was 86 14±2 95 ng/ml and the degree of fluctuation (DF) was 140 6±13 5% at steady state. Two one sided tests were performed in bioequivalence assessment. The results showed that the sustained release tablets were basically bioequivalent to the immediate release (IR) tablets on sale.展开更多
基金This work was supported by the National Research Foundation of South Korea(NRF)grants funded by the South Korean government(MEST)(No.2022R1A2C2004197,RS-2024-00407053 and RS-2023-00208448).
文摘While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.
基金supported by the National Natural Science Foundation of China(82274313)Key R&D Program of Shaanxi Province(2023GHZD43).
文摘Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.
文摘In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary modes of treatment. CurCousin<sup>®</sup> is a nutritional ingredient containing bioactive Calebin A, (analog of Curcumin) with self-affirmed GRAS status. CurCousin<sup>®</sup> has been a clinically studied dietary supplement ingredient with a positive impact on body weight, lipid levels and metabolic health. Bioenhancers play an important role in increasing the bioavailability of the active in turn enhancing efficacy as well as reducing the dosage required to achieve the therapeutic effect. This study investigated the possible pharmacokinetic interaction between CurCousin<sup>®</sup> at two different doses (2.25 and 4.5 mg/kg) in the presence and absence of BioPerine<sup>®</sup> (0.27 mg/kg), a natural bioenhancer in Sprague-Dawley rats. The results revealed that the addition of BioPerine<sup>®</sup> into CurCousin<sup>®</sup> (2.25 mg/kg) half the dose when administered enhances the bioavailability and was equipotent to CurCousin<sup>®</sup> (4.5 mg/kg) double the dose without BioPerine<sup>®</sup>. Thus, leading to future clinical studies to evaluate its improved pharmacological efficacy as well as reduced therapeutic dosage.
文摘Aim To investigate whether modified-release cefaclor capsules could lead to a more suitable pharmacokinetic profile in the plasma. Methods Cefaclor pellets were prepared by extrusion/spheronization and coated by Eudragit L30D-55 or Eudragit NE30D, then the two sorts of pellets were filled to capsules in a 35：65 ratio to made a modified-release （MR） capsules. The bioavailability of the MR capsules was studied in 24 healthy volunteers after oral administration in a fast state using a commercially available immediate release （IR） capsule as a reference. Results The results showed that the MR formulation had a relatively good bioavailability compared with the commercial capsules, as well as a longer time keeping drug level above MIC than immediate release capsule. The relative bioavailability of the MR capsules was 97.4- 12.1%. Conclusion The data of the present study indicate that time of cefaclor plasma concentration above MIC can be substantially prolonged if cefaclor is administered as a modified- release product.
文摘A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined by mass detector. The calibration curve of loratadine was linear within the range of 0.4～100 ng·mL -1 with r=0.9995 . The recovery of this method was within 95%～104%, within day and between day RSD were less than 12%. To study the pharmacokinetics and relative bioavailability of loratadine tablets, two formulations of loratadine tablets were given to 18 healthy male volunteers according to a randomized 2 way cross over design. The C max , AUC 0 t and T max values of the two formulations were 51.89±20.18 ng·mL -1 and 52.48±22.35 ng·mL -1 ; 140.75±88.42 ng·h·mL -1 and 147.24±92.33 ng·h·mL -1 ; 0.81±0.35 h and 0.81±0.27 h respectively. Results from statistic analysis showed that there were no significant difference between the C max , AUC 0-t and T max values of the two formulations. The relative bioavailability of tablets I with respect to tablets II was 97%±13% from the AUC 0 t measurement. Bioequivalance was observed between the two tablets.
文摘The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.
文摘A new pre-column derivation HPLC method with solid-phase extraction to determine captopril in human plasma was established. Derivation products were extracted by a solid-phase extraction method after the reagent, p-a-dibromoacetophenone(p-BPB), was added in the plasma samples. The samples were analyzed in a VP-ODS column with UV-detector. The calibration curve of captopril was linear within the range of 5~1000 ngmL-1 with r=0.9987, the recovery of this method was 98.652.04%, within day and between day RSD were no more than 3.4% and 8.4% respectively. To study the pharmacokinetics and the relative bioavailability of captopril tablets, two formulations of captopril tablets were given to 18 healthy male volunteers according to a randomized 2-way cross-over design with a 1-week washout period. The respective AUC0~6 , Cmax and Tmax values of the two formulations were 424.5125.7 and 439.4113.3 mghL-1; 505.9244.6 and 504.8172.2 mgL-1; 0.6620.181 and 0.5280.176 h. Results from statistics analysis showed that there were no significant difference between the AUC0~6 , Cmax and Tmax values of the two formulations, The relative bioavailability of tablets I with respect to II was 96.114.6% from AUC0~6 measurement. Bioequivalance was observed between the two tablets.
文摘Aim To establish a sensitive and specific liquid chromatography-mass spectrometry (HPLC-MS) method for measuring lovastatin level in human plasma and the relative bioavailability. Methods Lovastatin in the plasma was extracted with acetoacetate. Simvastatin was added as internal standard (IS). Samples were separated on a C_ 18 column with a mobile phase consisting of methanol and 50 mmol·L~ -1 sodium acetate (88 ∶ 12). The flow rate was 1 mL·min~ -1 . Sample was detected using an electrospray ionization (ES...
文摘The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.
文摘The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curcumin,a polyphenolic compound derived from turmeric,exhibits diverse pharmacological properties,including anti-inflammatory,antioxidant,and anticancer effects.Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms.This review examines the current literature on the interactions between curcumin and the gut microbiome.A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance.Key findings from studies exploring curcumin's efficacy in neurological disorders,gastrointestinal diseases,and metabolic dysfunction are synthesized and discussed.Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function,leading to beneficial effects on gut health and homeostasis.Mechanisms underlying curcumin's therapeutic effects include immune modulation,neuroprotection,and inflammation regulation.However,challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome.The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions.Further research is needed to optimize curcumin formulations,improve bioavailability,and address safety concerns.
文摘The aim of this study was to determine the apparent （AME） ＆ true （TMEn） metabolizable energy as well as the crude protein （CP） ＆ amino acid （AA） total tract （by excreta collection） digestibility （bioavailability） of field pea seeds （FPS） of the Greek cultivar ＂Olympos＂. Forty eight broilers were placed in individual cages and randomly allocated into 4 dietary treatments. Birds consumed 80 g/d of either a typical commercial diet or the same diet in which 100, 200 or 300 g/kg had been substituted by ground FPS. The experiment lasted 15 d. Apparent and true CP bioavailability of FPS were significantly decreased （P 〈 0.05） only at the inclusion rate of 300 g/kg. AA bioavailability remained at high levels （-0.80）, with the exception of methionine and valine and was similar to CP mean. The mean AME and TMEn values of FPS were estimated equal to 10.8 and 11.0 MJ ME/kg, respectively.
文摘The relative bioavailability of famotidine sustained release (SR) tablets was studied in 16 healthy male volunteers. Famotidine plasma concentration was determined by HPLC method, and the plasma concentration time data were processed with the method provided by USP XXIII. For single dose administration the peak plasma concentration occurring at 8 13±0 34 h was 69 52±3 00 ng/ml and the relative bioavailability was 112 4±8 6%. For multiple dose administration the peak plasma concentration of SR tablet was 86 14±2 95 ng/ml and the degree of fluctuation (DF) was 140 6±13 5% at steady state. Two one sided tests were performed in bioequivalence assessment. The results showed that the sustained release tablets were basically bioequivalent to the immediate release (IR) tablets on sale.
