水溶性依托泊苷前药磷酸依托泊苷（BMY-40481）的I期及药代动力学研究

Phase I and pharmacokinetic study of a water-soluble etoposide prodrug, etoposide phosphate (BMY-40481).

作者信息

Millward M J, Newell D R, Mummaneni V, Igwemezie L N, Balmanno K, Charlton C J, Gumbrell L, Lind M J, Chapman F, Proctor M

机构信息

University Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.

出版信息

Eur J Cancer. 1995 Dec;31A(13-14):2409-11. doi: 10.1016/0959-8049(95)00331-2.

DOI:10.1016/0959-8049(95)00331-2

PMID:8652278

Abstract

Etoposide phosphate is a water-soluble prodrug of etoposide. A phase I and pharmacokinetic study has been performed over the dose range 25-110 mg/m2/day for 5 days (etoposide equivalent doses). The maximum tolerated dose (MTD) was 110 mg/m2/day for 5 days every 3 weeks and the dose-limiting toxicity was neutropenia. Other toxicities were mild, with the exception of 2 patients who displayed significant hypersensitivity reactions. The etoposide phosphate:etoposide area under the plasma concentration versus time curve (AUC) ratio was < 1% and the pharmacokinetic parameters for etoposide were within previously reported ranges. Pharmacodynamic analyses demonstrated that etoposide AUC and baseline white blood cell count were significant determinants of leucopenia (model r2 = 0.51).

摘要

磷酸依托泊苷是依托泊苷的水溶性前体药物。已在25 - 110 mg/m²/天的剂量范围内进行了为期5天（依托泊苷等效剂量）的I期和药代动力学研究。最大耐受剂量（MTD）为每3周110 mg/m²/天，持续5天，剂量限制性毒性为中性粒细胞减少。除2例出现显著过敏反应的患者外，其他毒性均较轻。磷酸依托泊苷与依托泊苷的血浆浓度-时间曲线下面积（AUC）比值<1%，依托泊苷的药代动力学参数在先前报道的范围内。药效学分析表明，依托泊苷AUC和基线白细胞计数是白细胞减少的重要决定因素（模型r² = 0.51）。