一项关于体内多药耐药性（MDR）逆转的I期研究：硝苯地平加依托泊苷。
A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
作者信息
Philip P A, Joel S, Monkman S C, Dolega-Ossowski E, Tonkin K, Carmichael J, Idle J R, Harris A L
机构信息
ICRF Clinical Oncology Unit, Churchill Hospital, Oxford, UK.
出版信息
Br J Cancer. 1992 Feb;65(2):267-70. doi: 10.1038/bjc.1992.53.
Abstract
Multidrug resistance (MDR) is one of the mechanisms of resistance to multiple cytotoxic drugs and is mediated by the expression of a membrane pump called the P-glycoprotein. Nifedipine is one of the calcium channel blocking agents which reverses MDR in vitro. Fifteen patients with various malignancies received nifedipine at three dose levels: 40 mg, 60 mg and 80 mg orally twice daily for 6 days. Etoposide was administered intravenously on day 2 in a dose of 150-250 mg m-2 and orally 150-300 mg twice daily on days 3 and 4. Cardiovascular effects of nifedipine were dose limiting and the maximum tolerated dose was 60 mg bid. Mean area under the plasma concentration curve (AUC0-00) and plasma half-life (beta) of nifedipine and its major metabolite MI at the highest dose level were 7.87 microM.h, 7.97 h and 4.97 microM.h, 14.0 h respectively. Nifedipine did not interfere with the pharmacokinetics of etoposide.
摘要
多药耐药（MDR）是对多种细胞毒性药物产生耐药的机制之一，由一种名为P-糖蛋白的膜泵表达介导。硝苯地平是一种钙通道阻滞剂，可在体外逆转MDR。15例患有各种恶性肿瘤的患者接受了三个剂量水平的硝苯地平治疗：40毫克、60毫克和80毫克，每日口服两次，共6天。第2天静脉给予依托泊苷，剂量为150 - 250毫克/平方米，第3天和第4天每日口服两次，剂量为150 - 300毫克。硝苯地平的心血管效应具有剂量限制性，最大耐受剂量为每日两次60毫克。在最高剂量水平下，硝苯地平及其主要代谢产物M1的血浆浓度曲线下平均面积（AUC0 - ∞）和血浆半衰期（β）分别为7.87微摩尔·小时、7.97小时和4.97微摩尔·小时、14.0小时。硝苯地平不干扰依托泊苷的药代动力学。
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