de Valeriola D
Institut Jules Bordet, Unité d'Oncopharmacologie, Brussels, Belgium.
Anticancer Res. 1994 Nov-Dec;14(6A):2307-13.
Despite the fact that anthracyclines are one of the most commonly used and active classes of anticancer agents and that their pharmacokinetic behavior has been extensively studied, optimal anthracycline dosage regimens have not yet been defined. Only a few pharmacokinetic-pharmacodynamic (toxicity and response) relationships have been determined so far for anthracyclines and are here reviewed. The use of prolonged continuous infusion and fractionated schedules reduces doxorubicin cardiotoxicity but no sufficient data are available to date to demonstrate if those schedules result in equivalent antitumor efficacy to that achieved by IV bolus. Not enough data are available to conclude which is the best pharmacokinetic parameter to use in order to predict anthracycline-induced myelosuppression, other toxicities and/or clinical tumor response. Dosing adjustments of anthracyclines in the presence of liver dysfunction are still based on empirical guidelines instead of a more rational basis. Much work still remains to be done if we are to improve our knowledge of anthracyclines' pharmacodynamics. Limited sampling strategies will be of great help in the establishment of pharmacokinetic-pharmacodynamic relationships, which is essential to optimize the dosage regimen of anthracyclines in order to maximize their efficacy and/or minimize their toxicity in individual patients.
尽管蒽环类药物是最常用且有效的抗癌药物类别之一，并且其药代动力学行为已得到广泛研究，但最佳蒽环类药物给药方案尚未确定。迄今为止，仅确定了少数蒽环类药物的药代动力学-药效学（毒性和反应）关系，本文对此进行综述。延长持续输注和分次给药方案可降低阿霉素的心脏毒性，但目前尚无足够数据证明这些方案是否能产生与静脉推注相当的抗肿瘤疗效。没有足够的数据来确定使用哪个最佳药代动力学参数来预测蒽环类药物引起的骨髓抑制、其他毒性和/或临床肿瘤反应。肝功能不全时蒽环类药物的剂量调整仍基于经验指南，而非更合理的依据。如果我们要提高对蒽环类药物药效学的认识，仍有许多工作要做。有限采样策略将对建立药代动力学-药效学关系有很大帮助，这对于优化蒽环类药物的给药方案以在个体患者中最大化其疗效和/或最小化其毒性至关重要。
