Urinary excretion of paclitaxel and metabolites in a large series study

Abstract

Objective. Paclitaxel is an antineoplastic agent with significant activity against several tumour types. The major portion of the drug disposition (80-90%) in volves metabolism and biliary excretion. The purpose of this study was to investigate the relationships between the mean urinary paclitaxel excretion frac tion and the administered dose, creatinine clearance, or the measured paclitaxel area under the plasma concentration versus time curve. Design. The design used was a retrospective convenience sample study. Setting. The setting for this study was a hospi talised care center. Patients. A total of 103 24-hour urine collections from 60 patients treated with paclitaxel were used to investigate these relationships. Results. In this large series study, the paclitaxel urinary fraction was 5 ± 3% (mean ± SD) as a fraction of the administered paclitaxel dose. No correlations were found between the paclitaxel urinary excretion fraction and the administered dose, creatinine clear ance, and plasma concentration-time curve. In addi tion, the paclitaxel metabolites 6α-hydroxypaclitaxel, 3'- p-hydroxypaclitaxel and some unidentified com pounds were detected in the 24-hour urine samples of two patients, of whom one had a mild impaired renal function. Conclusions. Considering the low urinary ex cretion of paclitaxel, it is anticipated that patients with renal dysfunction require no dose adjustments. Metabolites were found in the urine.