A population pharmacokinetic model for doxorubicin and doxorubicinol in the presence of a novel MDR modulator, zosuquidar trihydrochloride (LY335979)
A population pharmacokinetic model for doxorubicin and doxorubicinol in the presence of a novel MDR modulator, zosuquidar trihydrochloride (LY335979)
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DOI：
10.1007/s00280-002-0542-3
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发表时间：
2003-02-01
影响因子：
3
通讯作者：
Aarons, L
中科院分区：
文献类型：
--
作者：
Callies, S;de Alwis, DP;Aarons, L
目的：在存在有效P-糖蛋白抑制剂zosuquidar.3HCl的情况下，开发多柔比星和多柔比星的群体药代动力学模型。方法：人口。使用方法（使用NONMEM实施）分析40例接受盐酸唑舒喹达和多柔比星静脉给药（分别在第1周期和第2周期同时给药，分别超过48 h和0.5 h）的患者的多柔比星-多柔比星药代动力学数据。结果如下：五房室药代动力学模型（包括多柔比星药代动力学的三个房室和多柔比星形成的两个途径）最好地描述了在存在佐舒喹达.3 HCl的情况下多柔比星-多柔比星的药代动力学。多柔比星清除率（CL）、外周分布容积（V2）和多柔比星表观清除率（CLm/fm）和表观分布容积（Vm/fm）分别为62.3 l/h、2360 l、143 l/h和3150 l，在不存在或存在低剂量zosuquidar.3HCl（
Purpose: To develop a population pharmacokinetic model for doxorubicin and doxorubicinol in the presence of zosuquidar.3HCl, a potent P-glycoprotein inhibitor. Methods: The population. approach was used (implemented with NONMEM) to analyse doxorubicin-doxorubicinol pharmacokinetic data from 40 patients who had received zosuquidar.3HCl and doxorubicin intravenously (separately in cycle I and concomitantly in cycle 2 over 48 h and 0.5 h, respectively). Results: A five-compartment pharmacokinetic model (including three compartments for doxorubicin pharmacokinetics with two pathways for doxorubicinol formation) best described the doxorubicin-doxorubicinol pharmacokinetics in the presence of zosuquidar.3HCl. Doxorubicin clearance (CL), peripheral volume of distribution (V2) and doxorubicinol apparent clearance (CLm/fm) and apparent volume of distribution (Vm/fm) were 62.3 l/h, 2360 1, 143 l/h and 3150 1, respectively, in the absence or presence of low doses of zosuquidar.3HCl (