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Urinary excretion of paclitaxel and metabolites in a large series study

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Hilde Rosing

Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Manon T Huizing

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Francesca J Koopman

Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Laurence JC van Warmerdam

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Wim W ten Bokkel Huinink

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

Jos H Beijnen

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands, Department of Pharmaceutical Analysis and Toxicology, Faculty of Pharmacy, State University of Utrecht, Utrecht, The Netherlands

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 6-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.

Journal of Oncology Pharmacy Practice, Vol. 4, No. 3, 159-164 (1998)
DOI: 10.1177/107815529800400304


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