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Abstract

Taxol metabolism. Isolation and identification of three major metabolites of taxol in rat bile.

B Monsarrat, E Mariel, S Cros, M Garès, D Guénard, F Guéritte-Voegelein and M Wright
Drug Metabolism and Disposition November 1990, 18 (6) 895-901;
B Monsarrat
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E Mariel
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S Cros
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M Garès
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D Guénard
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F Guéritte-Voegelein
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M Wright
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Abstract

The elimination of nonradioactive taxol in bile and urine was investigated in the rat after administration via the caudal vein (10 mg/kg). As in humans, no metabolites of taxol were detected by HPLC in rat urine, and only 10% of the injected taxol was recovered in urine over a 24-hr period. In contrast, 11.5% and 29% of the injected taxol was recovered in rat bile as unchanged taxol and metabolites, respectively. Among the nine taxol metabolites detected by HPLC, the side chain at C13, which is required for pharmacological activity, had been removed in only one minor metabolite, baccatin III. The chemical structures of the two major hydroxylated metabolites were determined by mass spectrometry (fast atom bombardment and desorption chemical ionization) and 1H-NMR spectroscopy. One was a taxol derivative hydroxylated on the phenyl group at C3' of the side chain at C13, while the other corresponded to a taxol derivative hydroxylated in the m-position on the benzoate of the side chain at C2. Although these two major taxol metabolites were as active as taxol in preventing cold microtubule disassembly, they were, respectively, 9 and 39 times less cytotoxic as taxol on in vitro L1210 leukemia growth. These results show for the first time that there is a significant hepatic metabolism of taxol.

 

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Drug Metabolism and Disposition
Vol. 18, Issue 6
1 Nov 1990
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Abstract

Taxol metabolism. Isolation and identification of three major metabolites of taxol in rat bile.

B Monsarrat, E Mariel, S Cros, M Garès, D Guénard, F Guéritte-Voegelein and M Wright
Drug Metabolism and Disposition November 1, 1990, 18 (6) 895-901;

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Abstract

Taxol metabolism. Isolation and identification of three major metabolites of taxol in rat bile.

B Monsarrat, E Mariel, S Cros, M Garès, D Guénard, F Guéritte-Voegelein and M Wright
Drug Metabolism and Disposition November 1, 1990, 18 (6) 895-901;
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