Population pharmacokinetics of low-dose paclitaxel in patients with brain tumors
作者:
Georg Hempel,
Christian Rübe,
Christina Mosler,
Marlies Wienstroer,
Alexandra Wagner-Bohn,
Andreas Schuck,
Normann Willich,
Joachim Boos,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 6
页码: 417-422
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: brain tumor;low-dose;paclitaxel;population pharmacokinetics;radiation
数据来源: OVID
摘要:
Our aim was to assess the pharmacokinetics of a low-dose schedule of paclitaxel in combination with radiation therapy in patients with brain tumors. Eighteen patients received 20–50 mg/m2paclitaxel as a 1-h infusion 18–24 h before radiation with 2 Gy on 5 consecutive days. In total, 156 plasma samples from 13 patients and 38 urine samples from nine patients were collected and analyzed by a validated capillary electrophoresis method. Data analysis was done using NONMEM with a two-compartmental model and proportional error model. No signs of non-linearity in the pharmacokinetic parameters were observed in this dosing range. The median cumulative urinary excretion was 2.4% (range 0.86–7.72%) of the given dose. Plasma clearance was found to be 6.71 l/h±70% and central volume of distribution was 3.64 l±79% (population mean ± interindividual variability, respectively). At the time of the radiation, i.e. 24 h after administration with the lowest dose of 20 mg/m2, the mean concentration of paclitaxel was 0.038 mg/l (0.045 μM) in plasma. We conclude that even with the lowest dose of 20 mg/m2paclitaxel, plasma concentrations at the time of radiation are achieved which are radiosensitizingin vitro.
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