Paclitaxel pharmacokinetics and pharmacodynamics

C. M. Kearns, L. Gianni, M. J. Egorin

Research output: Contribution to journalArticle

Abstract

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) displays nonlinear pharmacokinetics in humans. Both peak plasma paclitaxel concentrations and areas under the curve (AUCs) of the concentration versus time profiles will change disproportionately to changes in dose. Models that accurately describe the plasma paclitaxel profile contain two separate saturable processes, both described by Michaelis-Menten kinetics. Pharmacokinetic models using only linear components ultimately fail to describe adequately the disposition of paclitaxel in the body. The major toxicity of paclitaxel, neutropenia, appears to be related to the duration of time that plasma paclitaxel concentrations are at or above a threshold value. This relationship is well described by a sigmoid-E(max) (maximum effect) model. Neutropenia is not directly related to either peak paclitaxel plasma concentration or to paclitaxel areas under the curve. A relationship between therapeutic efficacy and paclitaxel disposition is, as yet, undefined.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalSeminars in Oncology
Volume22
Issue number3 SUPPL. 6
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Oncology

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    Kearns, C. M., Gianni, L., & Egorin, M. J. (1995). Paclitaxel pharmacokinetics and pharmacodynamics. Seminars in Oncology, 22(3 SUPPL. 6), 16-23.