Metabolism and pharmacology of taxoids

M. Wright, B. Monsarrat, I. Royer, E. K. Rowinsky, R. C. Donehower, T. Cresteil, D. Guénard

Research output: Contribution to journalArticlepeer-review

Abstract

This chapter presents metabolism and pharmacology of taxoids. Three main modifications occur in taxoids when they are introduced in the organism—namely, (1) epimerization, (2) hydrolysis, and (3) hydroxylation. After 72 h of incubation, the ratio of 7-epi-paclitaxel to paclitaxel varies from 0.36 to 0.48 in the cell and from 0.25 to 0.32 in the medium, depending on the cell line and on the initial concentration of paclitaxel. The epimerization of paclitaxel occurs in the medium in the presence or absence of cells. The reversible epimerization of the hydroxyl group at C-7 occurs with both paclitaxel and docetaxel. Two derivatives resulting from the hydrolysis of paclitaxel have been observed in human patients. Cleavage of the side chain at C-13 of the taxane ring results in the formation of baccatin III, while 10-deacetyl paclitaxel results from the cleavage of the acetyl group at the C-10 of the taxane ring. Hydroxylation is pharmacologically important, since hydroxylated compounds are the major metabolites of paclitaxel and docetaxel, leading in all cases to less cytotoxic derivatives which are readily eliminated.

Original languageEnglish (US)
Pages (from-to)131-164
Number of pages34
JournalPharmacochemistry Library
Volume22
Issue numberC
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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