van Gelder Teun
Department of Internal Medicine, University Hospital Rotterdam--Dijkzigt, Rotterdam, The Netherlands.
Drug Saf. 2002;25(10):707-12. doi: 10.2165/00002018-200225100-00003.
Tacrolimus is a drug for which therapeutic drug monitoring is recommended. The existence of a wide variety of potential drug interactions further supports the current strategy of measuring whole blood tacrolimus concentrations in transplanted patients. Cytochrome P450 (CYP)3A, the major phase I metabolising enzyme in humans, and the multi-drug efflux pump, P-glycoprotein, are present at high levels in the villus tip of enterocytes in the gastrointestinal tract. Oral bioavailability of tacrolimus can be increased by concomitant administration of inhibitors of either CYP3A or P-glycoprotein. CYP activity in the liver also influences tacrolimus concentrations. As a result, several drugs that are frequently being used in transplantation, such as corticosteroids and antifungal agents, will affect tacrolimus concentrations. Knowledge of such drug interactions is extremely important, as they may lead to clinically important under- or overexposure to tacrolimus, with acute rejection episodes or serious toxicity as a result.
他克莫司是一种建议进行治疗药物监测的药物。多种潜在药物相互作用的存在进一步支持了当前在移植患者中测量全血他克莫司浓度的策略。细胞色素P450（CYP）3A是人类主要的I相代谢酶，多药外排泵P-糖蛋白在胃肠道肠细胞的绒毛尖端大量存在。同时给予CYP3A或P-糖蛋白抑制剂可提高他克莫司的口服生物利用度。肝脏中的CYP活性也会影响他克莫司的浓度。因此，移植中常用的几种药物，如皮质类固醇和抗真菌剂，会影响他克莫司的浓度。了解此类药物相互作用极为重要，因为它们可能导致临床上他克莫司暴露不足或过量，进而引发急性排斥反应或严重毒性。
