IDENTIFICATION OF THE METABOLITES OF IRINOTECAN, A NEW DERIVATIVE OF CAMPTOTHECIN, IN RAT BILE AND ITS BILIARY-EXCRETION
IDENTIFICATION OF THE METABOLITES OF IRINOTECAN, A NEW DERIVATIVE OF CAMPTOTHECIN, IN RAT BILE AND ITS BILIARY-EXCRETION
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DOI：
10.3109/00498259109039556
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发表时间：
1991-09-01
期刊：
影响因子：
1.8
通讯作者：
HAKUSUI, H
中科院分区：
文献类型：
--
作者：
ATSUMI, R;SUZUKI, W;HAKUSUI, H
1. 为了研究新型喜树碱类似物伊立替康的代谢物和胆汁排泄，该药物通过静脉注射给药。给大鼠注射(10 mg/kg)，收集胆汁、尿液和粪便。2．通过 t.l.c. 在大鼠胆汁中发现未变化的伊立替康、代谢物 7-乙基-10-羟基喜树碱 (EHCPT) 和未知代谢物 M-1。和 h.p.l.c.来自 β-葡萄糖醛酸酶水解，n.m.r.经光谱和质谱鉴定，M-1被鉴定为EHCPT-葡萄糖醛酸苷（EHCPT Glu）。胆汁中的其他代谢物可以忽略不计。3．大鼠服用伊立替康后，胆汁和尿液累积放射性排泄分别为剂量的62.2%和33.3%，其中9.0%的放射性经粪便排出。4．大约。 24小时内排出的胆汁放射性物质中55%为原形伊立替康，22%为EHCPT Glu，9%为EHCPT。5。大约。 18%的胆汁放射性被肠道重吸收。
1. To investigate the metabolites and biliary excretion of new camptothecin analogue, irinotecan, the drug was administered i.v. to rats (10 mg/kg) and bile, urine and faeces were collected.2. In rat bile, unchanged irinotecan, the metabolite 7-ethyl-10-hydroxycamptothecin (EHCPT) and unknown metabolite M-1 were found by t.l.c. and h.p.l.c. From beta-glucuronidase hydrolysis, n.m.r. spectrometry and mass spectrometry, M-1 was identified as EHCPT-glucuronide (EHCPT Glu). Other metabolites in the bile were negligible.3. The cumulative biliary and urinary excretion of radio activity after dosage of rats with irinotecan were 62.2% and 33.3% dose, respectively, and 9.0% of the radioactivity was excreted in the faeces.4. Approx. 55% of the biliary radioactivity excreted in 24 h was unchanged irinotecan, 22% was EHCPT Glu, and 9% was EHCPT.5. Approx. 18% of the biliary radioactivity was reabsorbed from the intestine.