代谢物
紫杉烷
排泄
新陈代谢
羟基化
药理学
医学
药物代谢
内科学
药品
内分泌学
化学
生物化学
癌症
酶
乳腺癌
作者
Bernard Monsarrat,Paul Alvinerie,M. Wright,Jean-Bernard Dubois,Francoise Gueritte-Voegelein,Daniel Guenard,Ross C. Donehower,Eric K. Rowinsky
出处
期刊:Journal of The National Cancer Institute Monographs
[Oxford University Press]
日期:1993-01-01
卷期号: (15): 39-46
被引量:37
摘要
To date there have been limited studies of the metabolism and disposition of Taxol in animals and humans. Renal disposition of unmetabolized Taxol has been documented to account for a maximum of 5% to 10% of an administered dose of Taxol in humans, but the principal processes involved in drug disposition, particularly the roles of biliary excretion and drug metabolism, have not been evaluated. Therefore, the biliary excretion of Taxol has been studied in rats and in a human patient receiving Taxol in a phase I trial. Of the total doses administered to rats and the patient, 40% and 20%, respectively, were excreted in the bile in the forms of unmetabolized Taxol and Taxol metabolites until 24 hours posttreatment. Although the biliary excretion of unmetabolized Taxol accounted for 10% and 3% of total drug disposition in the rats and in the patient, respectively, the remaining portion consisted of several metabolites. Nine metabolites were detected in rat bile, and five metabolites were detected in human bile. The chemical structures of four of the rat metabolites and three of the human metabolites have been identified thus far. With the exception of baccatin III, a minor metabolite found only in rat bile that lacks the side chain at C-13 position of the taxane ring, the other metabolites were monohydroxylated or dihydroxylated and had intact taxane rings and side chains at taxane ring positions C-2 and C-13. The taxane ring and both the C-2 and C-13 side chains were susceptible to hydroxylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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