Rowinsky E K
Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Centre, Baltimore, Maryland 21287-8934, USA.
J Infus Chemother. 1995 Fall;5(4):173-8.
The comprehensive development of new antineoplastic agents mandates a thorough evaluation of schedule-dependent cytotoxicity and toxicity. This report focuses on the topoisomerase I inhibitors as an example of a novel class of anticancer agents in exposure duration may be a critical factor in the achievement of an optimal therapeutic index. The mechanistic and pharmacologic determinants and rationale for using protracted exposure schedules in administering several topoisomerase I inhibitors are discussed. The review also discusses dihydropyrimidine dehydrogenase as a pharmacologic target, enabling administration of oral fluoropyrimidines.
新型抗肿瘤药物的全面发展要求对剂量依赖性细胞毒性和毒性进行彻底评估。本报告以拓扑异构酶I抑制剂为例，这类新型抗癌药物的暴露持续时间可能是实现最佳治疗指数的关键因素。文中讨论了在使用几种拓扑异构酶I抑制剂时采用延长暴露方案的机制、药理学决定因素及原理。该综述还讨论了二氢嘧啶脱氢酶作为一个药理学靶点，使得口服氟嘧啶类药物得以应用。
