Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data
Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data
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DOI：
10.1007/s00228-003-0636-9
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发表时间：
2003-09-01
影响因子：
2.9
通讯作者：
Masimirembwa, CM
中科院分区：
文献类型：
--
作者：
Li, XQ;Björkman, A;Masimirembwa, CM
Objective.了解抗寄生虫药物（APD）的代谢将有助于在临床实践中不断努力优化剂量建议。本研究旨在进一步鉴定代谢主要APD的细胞色素P-450（CYP）酶，并评估从体外数据预测体内药物清除率的可能性。在体外系统中，大鼠和人的肝微粒体（RLM，HLM）和重组细胞色素P-450（rP 450），被用来确定的内在清除率（克林特）和确定负责CYP和它们的相对贡献，在15个常用的APDs.Results和讨论的代谢。在RLM和HLM中测定的克林特显示较低（r（2）=0.50）但显著（P <70%肝血流量;阿莫地喹，吡喹酮，阿苯达唑，噻苯达唑），低清除率药物（
Objective. Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P-450 (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vivo drug clearances from in vitro data.Methods. In vitro systems, rat and human liver microsomes (RLM, HLM) and recombinant cytochrome P-450 (rCYP), were used to determine the intrinsic clearance (CLint) and identify responsible CYPs and their relative contribution in the metabolism of 15 commonly used APDs.Results and discussion. CLint determined in RLM and HLM showed low (r(2)=0.50) but significant (P70% liver blood flow; amodiaquine, praziquantel, albendazole, thiabendazole), low-clearance drugs (