Hebert Mary F, Blough David K, Townsend Robert W, Allison Mark, Buell Donald, Keirns James, Bekersky Ihor
University of Washington, Department of Pharmacy, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA.
J Clin Pharmacol. 2005 Sep;45(9):1018-24. doi: 10.1177/0091270005279274.
Tacrolimus is an approved immunosuppressive agent and a known substrate for CYP3A. Micafungin is an echinocandin antifungal agent and a mild inhibitor of CYP3A metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of tacrolimus (5 mg oral) and micafungin (100 mg intravenous) alone and with concomitant administration (n=26). Tacrolimus area under the concentration-time curve was 298+/-135 microgh/L when tacrolimus was administered alone, 305+/-129 microgh/L (P=.8; confidence interval 89%, 118%) when tacrolimus was given with single-dose micafungin, and 282+/-138 microg*h/L (P=.4; confidence interval 82%, 107%) when tacrolimus was given with steady-state micafungin. Despite the mild inhibition of CYP3A in vitro by micafungin, there does not appear to be a drug interaction with tacrolimus and micafungin either with single-dose or steady-state micafungin administration.
他克莫司是一种已获批准的免疫抑制剂,也是已知的细胞色素P450 3A(CYP3A)底物。米卡芬净是一种棘白菌素类抗真菌药,在体外是CYP3A代谢的轻度抑制剂。本研究的目的是评估单独使用以及联合给药时(n = 26)他克莫司(口服5 mg)和米卡芬净(静脉注射100 mg)的药代动力学。单独给予他克莫司时,他克莫司浓度-时间曲线下面积为298±135μg·h/L;给予单剂量米卡芬净时,他克莫司浓度-时间曲线下面积为305±129μg·h/L(P = 0.8;置信区间89%,118%);给予稳态米卡芬净时,他克莫司浓度-时间曲线下面积为282±138μg·h/L(P = 0.4;置信区间82%,107%)。尽管米卡芬净在体外对CYP3A有轻度抑制作用,但无论给予单剂量还是稳态米卡芬净,他克莫司与米卡芬净之间似乎都不存在药物相互作用。