钙调神经磷酸酶抑制剂体内处置的临床决定因素及机制研究进展  

Advances in clinical determinants and mechanisms of calcineurin inhibitor pharmacokinetic disposition in vivo

作　　者：张璐 李晶洁[2] 闫佳佳[1] 王长希[3] 黄民[4] 陈孝[1] 陈攀[1] ZHANG Lu;LI Jing-jie;YAN Jia-jia;WANG Chang-xi;HUANG Min;CHEN Xiao;CHEN Pan(Dept of Pharmacy,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Reproductive Medicine Center, The Six Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China;Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China;Institute of Clinical Pharmacology,Sun Yat-sen Universit,Guangzhou 510080)

机构地区：[1]中山大学附属第一医院药学部,广东广州510080 [2]中山大学附属第六医院生殖医学中心,广东广州510655 [3]中山大学附属第一医院器官移植中心,广东广州510080 [4]中山大学临床药理研究所,广东广州510080

出　　处：《中国药理学通报》2022年第4期496-500,共5页Chinese Pharmacological Bulletin

基　　金：广东省基础与应用基础研究基金项目(No 2020A1515010138);国家重点研发计划资助(No 2017YFC0909900)。

摘　　要：钙调神经磷酸酶抑制剂(calcineurin inhibitor,CNI)他克莫司和环孢素是广泛使用的免疫抑制药物,具有个体内和个体间的药动学和药效学变异性大的特性。CNI的亲脂性高,经历广泛的首过代谢,是肠道和肝脏中细胞色素P450(cytochrome P450,CYP)3A4、CYP3A5以及P-糖蛋白(P-glycoprotein,P-gp)转运体的底物。该酶和转运体的功能是由基因多态性、药物和内源性物质(如炎症因子)的诱导或抑制导致的复杂相互作用决定。该文系统总结CNI体内处置变异性的常见临床决定因素,包括腹泻和其他肠道疾病、贫血、低蛋白血症、高脂血症、肝和肾脏疾病、联合用药等,并讨论潜在的影响机制。Tacrolimus and cyclosporine are both calcineurin inhibitors(CNI)that widely used for immunosuppression and have the characteristics of great intra-and inter-variabilities in pharmacokinetics and pharmacodynamics.CNI undergoes extensive first-pass metabolism and is substrate for cytochrome P450(CYP)3A4,CYP3A5 and P-glycoprotein in intestine and liver.The functions of the enzyme and transporter are determined by complex interactions including gene polymorphisms,induction or inhibition of drugs and endogenous substances(such as inflammatory factors).This review summarizes the clinical determinants of CNI treatment variability,including food intake,diarrhea and other intestinal diseases,anemia,hypoproteinemia,hyperlipidemia,liver and kidney disease and combination medications.The underlying mechanisms are also discussed.

关 键 词：钙调神经磷酸酶抑制剂 他克莫司 环孢素 药代动力学 CYP450酶 P-糖蛋白 

分 类 号：R341.32[医药卫生—基础医学] R345.61