摘要
目的：研究注射用伏立康唑前药（FLKZQY）在雌、雄大鼠中代谢及毒性差异,并观察SD大鼠体内性激素水平的变化对伏立康唑前药在大鼠体内代谢的影响,为其进一步临床应用提供依据。方法：选取5～6周龄SD大鼠,随机分成去势与伪手术组,雌、雄分开分组（雌、雄各半,每组8只）,手术后恢复3 d,然后连续7 d静脉注射120 mg·kg-1·d-1伏立康唑前药,于第7天进行眼眶采血。采用毒代动力学试验、酶联免疫吸附试验（ELISA）法,检测其代谢及毒性差异。结果：毒代动力学结果显示,伪手术雌鼠药时曲线下面积（AUC）、最大血药浓度（Cmax）、半衰期（t1/2）均高于伪手术雄鼠;去势雌鼠最大血药浓度（Cmax）、半衰期（t1/2）均较伪手术雌鼠显著性降低（P〈0.05）,药时曲线下面积（AUC）极其显著性降低（P〈0.01）;去势雄鼠受试物组与伪手术雄鼠受试物组相比药时曲线下面积（AUC）、半衰期（t1/2）、最大血药浓度（Cmax）则升高,其中AUC与Cmax差异显著（P〈0.05）;ELISA结果显示中,与伪手术雌鼠相比,去势雌鼠的肝脏细胞色素P450同工酶CYP2C19、CYP2C9以及CYP3A4含量均明显增加（P〈0.05）,去势雄鼠与伪手术雄鼠相比P450同工酶含量降低,但未达到统计学差异。结论：在本试验条件下,注射用伏立康唑前药在雌、雄大鼠体内的代谢存在性别差异。而性激素水平可能通过调节伏立康唑相关代谢酶水平从而对伏立康唑代谢产生影响。
OBJECTIVE To investigate metabolism and toxicity of FLKZQY for injection.Toxicokinetic test was used to analyze concentration of drugs in castrated rats to provide a safety evaluation for further clinical application.METHODS SD rats of 5-6 weeks were randomly divided into castrated and sham groups（half male and half female,8in each group）.After 3 days of recovery post operation,120 mg·kg-1·d-1 FLKZQY was intravenously administered consecutively for 7 days,and orbital venous blood was collected on seventh day.Toxicokinetic test method and enzyme linked immunosorbent assay（ELISA）test were perform to test differences of metabolism and toxicity.RESULTS Toxicokinetic results showed that,AUC,t1/2and Cmax of female rats were higher than male rats in sham group.AUC,t1/2and Cmaxof sham rats were higher than ovariectomized rats in female group（P〈0.01）.AUC,t1/2and Cmax of sham rats were lower than castrated rats in male group（P〈0.05）.In ELISA test,enzyme contents of sham rats were higher compared with ovariectomized rats in female group（P〈0.05）.Enzyme contents of castrated rats were lower than sham rats in male group,but no statistically significant difference was found.CONCLUSION Under experimental conditions of this study,expression of FLKZQY in rats have obvious gender differences,while sex hormones can produce effects on FLKZQY metabolism by regulating levels of relevant metabolism enzymes of FLKZQY.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2016年第18期1563-1566,共4页
Chinese Journal of Hospital Pharmacy
