Taxol metabolism in rat hepatocytes

Thomas Walle, Gondi N. Kumar, Joellyn M. McMlllan, Kelly R. Thornburg, U. Kristina Walle

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Metabolism of the anticancer drug taxol was investigated in freshly isolated rat hepatocytes. Two main metabolites were separated by reversed-phase HPLC and shown by tandem mass spectrometry to be monohydroxylated metabolites. Kinetic studies revealed apparent Km values of 68 and 61 μM with identical Vmax values for the two metabolites. Verapamil and midazolam, but not phenacetin, showed concentration-dependent inhibition of taxol metabolism with both metabolites being affected equally. The ic50 was about 100 μM for verapamil and 25 μM for midazolam. These observations demonstrate for the first time in vitro metabolism of taxol and suggest that the metabolism may be subject to potentially important interactions with numerous other drugs.

Original languageEnglish (US)
Pages (from-to)1661-1664
Number of pages4
JournalBiochemical Pharmacology
Volume46
Issue number9
DOIs
StatePublished - Nov 2 1993

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Metabolites
Paclitaxel
Metabolism
Rats
Hepatocytes
Midazolam
Verapamil
Phenacetin
Enzyme inhibition
Tandem Mass Spectrometry
Pharmaceutical Preparations
Inhibitory Concentration 50
Mass spectrometry
High Pressure Liquid Chromatography
Kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Walle, T., Kumar, G. N., McMlllan, J. M., Thornburg, K. R., & Walle, U. K. (1993). Taxol metabolism in rat hepatocytes. Biochemical Pharmacology, 46(9), 1661-1664. https://doi.org/10.1016/0006-2952(93)90336-U

Taxol metabolism in rat hepatocytes. / Walle, Thomas; Kumar, Gondi N.; McMlllan, Joellyn M.; Thornburg, Kelly R.; Walle, U. Kristina.

In: Biochemical Pharmacology, Vol. 46, No. 9, 02.11.1993, p. 1661-1664.

Research output: Contribution to journalArticle

Walle, T, Kumar, GN, McMlllan, JM, Thornburg, KR & Walle, UK 1993, 'Taxol metabolism in rat hepatocytes', Biochemical Pharmacology, vol. 46, no. 9, pp. 1661-1664. https://doi.org/10.1016/0006-2952(93)90336-U
Walle, Thomas ; Kumar, Gondi N. ; McMlllan, Joellyn M. ; Thornburg, Kelly R. ; Walle, U. Kristina. / Taxol metabolism in rat hepatocytes. In: Biochemical Pharmacology. 1993 ; Vol. 46, No. 9. pp. 1661-1664.
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