Hrushesky W J
Stratton V.A. Medical Center, Albany, NY 12208.
Clin Chem. 1993 Nov;39(11 Pt 2):2413-8.
Circadian variation in drug metabolism and tissue sensitivity to drugs affects their activity and toxicity. A growing body of data suggests that therapy may be improved and toxicity reduced by administering antineoplastic agents at carefully selected times of the day. Here I briefly review molecular, cellular, and organismic time-keeping mechanisms as well as cytokinetic, pharmacokinetic, and pharmacodynamic data, which support the predictable and exploitable nonlinear dynamic relation between dose and effect that occurs each day.
药物代谢和组织对药物敏感性的昼夜变化会影响药物的活性和毒性。越来越多的数据表明,通过在一天中精心选择的时间给予抗肿瘤药物,治疗效果可能会得到改善,毒性也会降低。在此,我简要回顾分子、细胞和机体的计时机制,以及细胞动力学、药代动力学和药效学数据,这些数据支持了每天都会出现的剂量与效应之间可预测且可利用的非线性动态关系。