Drug interactions of paclitaxel metabolism in human liver microsomes.

The human liver metabolism of paclitaxel (Taxol), an anticancer drug, leads to three metabolites: 6alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6alpha,3'-p-dihydroxypaclitaxel. The inter-individual variability of paclitaxel metabolism was investigated first in vitro using 22 human liver microsomes. Three metabolites have been detected by HPLC.

Individual dosing of carboplatin based on drug monitoring in children receiving high-dose chemotherapy.

Individual dosing of carboplatin based on drug monitoring was performed within a multi-centric phase I study based on high AUC-levels in children. Twelve patients (aged 3-17 years old) have been included: 3, 5, and 4 patients at the overall target ultrafilterable carboplatin AUC of 20, 25, or 30 mg/ml x min, respectively. Carboplatin was administered as a daily 60-min infusion, repeated on five consecutive days.

Phase I and pharmacokinetic study of escalating dose of docetaxel administered with granulocyte colony-stimulating factor support in adult advanced solid tumors.

Purpose: The purpose of our study was to assess the feasibility, toxicity, and pharmacokinetics of an escalating dose of docetaxel when administered with granulocyte colony-stimulating factor (G-CSF) support every 3 weeks.

Experimental Design: Patients with advanced solid malignancies were treated with escalating doses of docetaxel as a 1-h infusion every 3 weeks, supported by s.c.

Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity.

The combination of 5-fluorouracil-folinic acid and oxaliplatin has led to a significant improvement of chemotherapy efficacy in advanced pretreated colorectal cancer. The objective of the present study was, considering the oxaplatin-5-fluorouracil-folinic acid combination, to examine the impact of one given drug on the cellular determinants of cytotoxic activity of the other drug. These cellular factors were analysed on the human colon cancer cell line WiDr in clinically relevant conditions of drug exposure ('De Gramont' schedule) with oxaliplatin-folinic acid during 2 h followed by 5-fluorouracil 48 h.

Rapid high-performance liquid chromatographic determination of docetaxel (Taxotere) in plasma using liquid-liquid extraction.

A new rapid and sensitive high-performance liquid chromatographic method for analysis of docetaxel (Taxotere) in human plasma was developed and validated. After adding an internal standard (paclitaxel, Taxol), plasma was extracted following a simple liquid-liquid extraction with diethyl ether. Extraction efficiency averaged 95% for docetaxel.