TAXOL METABOLISM IN RAT HEPATOCYTES

Metabolism of the anticancer drug taxol was investigated in freshly is olated rat hepatocytes. Two main metabolites were separated by reverse d-phase HPLC and shown by tandem mass spectrometry to be monohydroxyla ted metabolites. Kinetic studies revealed apparent K(m) values of 68 a nd 61 muM with identical V(max) values for the two metabolites. Verapa mil and midazolam, but not phenacetin, showed concentration-dependent inhibition of taxol metabolism with both metabolites being affected eq ually. The IC50 was about 100 muM for verapamil and 25 muM for midazol am. These observations demonstrate for the first time in vitro metabol ism of taxol and suggest that the metabolism may be subject to potenti ally important interactions with numerous other drugs.