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目的:对不同人群环孢素A(CSA)的药动学及其主要影响因素进行综述,为临床实施CSA个体化用药方案提供参考。方法:以“Cyclosporine”“Pharmacokinetic”“Interaction”“环孢素A”“临床应用”等组合作为关键词,查阅1985-2014年Pub Med、中国医院知识总库等数据库中环孢素的药动学及相关影响因素的文献,并据此进行归纳和总结。结果:共查询到文献1 146条,其中有效文献31条。结果表明,不同年龄、种族、性别、遗传基因型和处于不同机体状态的人群,CSA在其体内的血药浓度、清除率(CL)等药动学参数存在显著差异。胆囊切除、肝硬化、肥胖手术等病理状态和细胞色素P45(0CYP)3A4酶抑制剂、P糖蛋白底物抑制剂联用时,均可升高CSA的血药浓度;促胃肠动力药、CYP3A4酶诱导剂、P糖蛋白底物诱导剂等联用时,可明显降低CSA的血药浓度。结论:CSA的药动学受多种因素影响。在未来的临床工作中,除了应加大CSA的血药浓度监测,还需开展相关基因型多态性的检测技术,以便及时调整CSA的给药剂量,促进临床个体化与合理用药。
OBJECTIVE: To summarize the pharmacokinetics of cyclosporin A (CSA) in different populations and its main influential factors, and to provide a reference for the clinical implementation of CSA individualized drug regimen. METHODS: A combination of “Cyclosporine”, “Pharmacokinetic”, “Interaction”, “Ciclosporin A” and “Clinical Application” was used as a key word to refer to Pub Med from 1985 to 2014, Library and other databases cyclosporine pharmacokinetics and related factors of literature, and accordingly summarized and summarized. Results: A total of 1 146 articles were found, of which 31 were valid documents. The results showed that there were significant differences in the pharmacokinetic parameters such as plasma concentration and clearance (CL) of CSA in different age, race, gender, genotype and in different body states. Cholecystectomy, cirrhosis, obesity surgery and other pathological conditions and cytochrome P45 (0CYP) 3A4 enzyme inhibitors, P-glycoprotein substrate inhibitors, can increase CSA plasma concentration; promote gastrointestinal motility drug, CYP3A4 Enzyme inducer, P-glycoprotein substrate inducer, etc., can significantly reduce the blood concentration of CSA. Conclusion: The pharmacokinetics of CSA is influenced by many factors. In the future clinical work, in addition to monitoring blood concentration of CSA should be increased, but also to carry out the detection of genotypic polymorphisms in order to timely adjust the dosage of CSA to promote clinical individual and rational drug use.