Comandone A, Leone L, Oliva C, Frustaci S, Monteleone M, Colussi A M, Dal Canton O, Bergnolo P, Boglione A, Bumma C
Department of Clinical Oncology, San Giovanni Antica Sede Hospital, Turin, Italy.
J Chemother. 1998 Oct;10(5):385-93. doi: 10.1179/joc.1998.10.5.385.
Ifosfamide is a leading drug in soft tissue sarcoma therapy. Recently high dose therapy (>9 g/m2) has been introduced in different schemes to obtain a higher response rate. All these higher doses can be administered following two different schedules: continuous infusion 24 hours a day for 4-5 days or bolus administration for 5 consecutive days. In this study we compare the differences in the pharmacokinetic profile between the two schedules. In both schemes we saw a very important autoinduction phenomenon, with a corresponding half-life decrease and total body clearance increase during the days of therapy. The clearances were not directly correlated with the administered dose. We can conclude that ifosfamide continuous infusion therapy is equivalent to fractionated administration, at least from a pharmacokinetic point of view. Short-term infusion is subjectively better tolerated and is therefore preferred.
异环磷酰胺是软组织肉瘤治疗中的一种主要药物。最近，高剂量疗法（>9 g/m²）已被引入不同方案以获得更高的缓解率。所有这些更高剂量都可以按照两种不同的给药方案进行给药：每天持续输注24小时，共4 - 5天，或连续5天进行大剂量推注给药。在本研究中，我们比较了两种给药方案之间药代动力学特征的差异。在两种方案中，我们都观察到了非常重要的自身诱导现象，在治疗期间相应的半衰期缩短，全身清除率增加。清除率与给药剂量无直接相关性。我们可以得出结论，至少从药代动力学角度来看，异环磷酰胺持续输注疗法等同于分次给药。短期输注在主观上耐受性更好，因此更受青睐。
