代谢物
药代动力学
尿
排泄
药理学
化学
粪便
新陈代谢
顺铂
高效液相色谱法
内科学
化疗
色谱法
生物
医学
生物化学
古生物学
作者
Thomas Walle,U K Walle,Gondi Kumar,Kapil N. Bhalla
出处
期刊:PubMed
日期:1995-04-01
卷期号:23 (4): 506-12
被引量:47
摘要
The objective of this study was to determine the metabolic fate and disposition of taxol in cancer patients. Five patients received 225 or 250 mg/m2 of taxol together with 100 microCi of [3H]taxol as a 3-hr infusion, followed by cisplatin and 5-fluorouracil. Urine, feces, and blood samples were collected for 120 hr and analyzed for total radioactivity, taxol, and metabolites by reversed-phase HPLC and tandem MS. Total urinary excretion was 14.3 +/- 1.4% (SE) of the dose, with unchanged taxol and an unknown polar metabolite as the main excretion products. Total fecal excretion was 71.1 +/- 8.2%, with 6 alpha-hydroxytaxol being the largest component by far. Unchanged taxol and four other metabolites could also be identified from fecal extracts. The plasma area under the curve for unchanged taxol was 20.5 +/- 2.3 microM.hr and that for total taxol metabolites was 14.2 +/- 4.5 microM.hr. The half-life of total metabolites (5.6 +/- 0.4 hr), however, greatly exceeded that of unchanged taxol (2.9 +/- 0.3 hr). Thus, at 5-hr posttaxol infusion, the plasma concentrations of the five metabolites together exceeded the taxol concentration by 2.4-fold. The findings from this study should be of importance as a guide to further therapeutic evaluation of this drug.
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