The pharmacokinetics of a 1-h paclitaxel infusion

被引：50

作者：

Mross K. ^{[1
]}

Holländer N. ^{[2
]}

Hauns B. ^{[1
]}

Schumacher M. ^{[2
]}

Maier-Lenz H. ^{[1
]}

机构：

[1] Department of Medical Oncology and Clinical Pharmacology, Tumor Biology Center at the Albert-Ludwigs-University Freiburg, 79106 Freiburg

[2] Institute of Medical Biometry and Medical Informatics, Albert-Ludwigs-University

来源：

Cancer Chemotherapy and Pharmacology | 2000年 / 45卷 / 6期

关键词：

Paclitaxel; Pharmacokinetics; Toxicity;

D O I：

10.1007/s002800051020

中图分类号：

学科分类号：

摘要：

Purpose: To characterize the disposition of paclitaxel (PAC) after a 1-h infusion in humans and define if possible a pharmacodynamic relationship between PAC disposition and the observed toxicity. Patients and methods: PAC pharmacokinetics were studied in 43 courses of therapy in 30 patients (30 first course, 13 PK third course). PAC was administered at 150, 175, 200, 225 and 250 mg/m2 by a 1-h infusion to patients with advanced cancer (lung, breast, ovarian, cervix, and head and neck). PAC was quantified by high- performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated by noncompartmental and model-dependent methods. Results: Increases in the area under the curve and the peak plasma concentration were not proportional to increases in the dose. However, the deviation from linearity is rather moderate. The dose-limiting toxicity was central neuropathy which was not associated with pharmacokinetic deviations. Owing to the absence of grade 3 or 4 myelotoxicity, no clear correlation between this toxicity and pharmacokinetic parameters could be established. Conclusion: Within the evaluated dose range of the 1-h infusion there was only a moderate nonlinear disposition of PAC in humans and therefore a dose of 225 mg/m2 is recommended as safe. The observation of central neuropathy could not be directly related to a pharmacokinetic parameter. The complexity of the formulation which included Cremophor EL and ethanol may offer an explanation for the observed central neurotoxicity.

引用

页码：463 / 470

页数：7

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