title: Identification of the metabolites of irinotecan, a new derivative of camptothecin, in rat bile and its biliary excretion.
abstract: 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 radioactivity 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.
authors.affiliation: Research Institute, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Atsumi
authors.forename: W
authors.initials: W
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Hakusui
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004764:Enterohepatic Circulation; D005243:Feces / Q000737:chemistry; D005966:Glucuronidase; D006868:Hydrolysis; D007410:Intestinal Diseases / Q000139:chemically induced; D000077146:Irinotecan; D007783:Lactones / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence
chemical_list: D007783:Lactones; D000077146:Irinotecan; D005966:Glucuronidase; D002166:Camptothecin