BIOAVAILABILITY OF CYCLOSPORINE WITH CONCOMITANT RIFAMPIN ADMINISTRATION IS MARKEDLY LESS THAN PREDICTED BY HEPATIC ENZYME-INDUCTION
BIOAVAILABILITY OF CYCLOSPORINE WITH CONCOMITANT RIFAMPIN ADMINISTRATION IS MARKEDLY LESS THAN PREDICTED BY HEPATIC ENZYME-INDUCTION
复制标题
DOI：
10.1038/clpt.1992.171
复制
发表时间：
1992-11-01
影响因子：
6.7
通讯作者：
BENET, LZ
中科院分区：
文献类型：
--
作者：
HEBERT, MF;ROBERTS, JP;BENET, LZ
在6名健康志愿者中研究了环孢霉素口服（10 mg/kg）和静脉注射（3 mg/kg）后的药代动力学，并与利福平合用。分析血液和血浆（在37 ℃下分离）样品的环孢素浓度。对于血液和血浆，环孢素的清除率分别计算为0.30和0.55 L/hr/kg，稳态分布容积值为1.31和1.68 L/kg，利福平给药前阶段的生物利用度为27%和33%。环孢素的利福平后清除率为0.42和0.79 L/hr/kg，稳态分布容积值为1.36和1.35 L/kg，血液和血浆的生物利用度分别为10%和9%。利福平不仅诱导环孢素的肝脏代谢，而且降低其生物利用度的程度比代谢增加所预测的更大。生物利用度降低最可能的原因是肠细胞色素P450酶的诱导，其似乎明显大于肝代谢的诱导。
The pharmakinetics of cycloporine was studied in six healthy volunteers after administration of the drug orally (10 mg/kg) and intravenously (3 mg/kg) with and without concomitant rifampin administration. Both blood and plasma (separated at 37-degrees-C) samples were analyzed for cyclosporine concentration. For blood and plasma, respectively, clearances of cyclosporine were calculated to be 0.30 and 0.55 L/hr/kg, values for volume of distribution at steady state were 1.31 and 1.68 L/kg, and bioavailabilities were 27% and 33% during the pre-rifampin phase. Post-rifampin phase clearances of cyclosporine were 0.42 and 0.79 L/hr/kg, values for volume of distribution at steady state were 1.36 and 1.35 L/kg, and bioavailabilities were 10% and 9% for blood and plasma, respectively. Rifampin not only induces the hepatic metabolism of cyclosporine but also decreases its bioavailability to a greater extent than would be predicted by the increased metabolism. The decreased bioavailability most probably can be explained by an induction of intestinal cytochrome P450 enzymes, which appears to be markedly greater than the induction of hepatic metabolism.