Studies on the Metabolic Fate of CPT-11. (3): Pharmacokinetics in Rats following a single intravenous administration of 14C-CPT-11 (PP).
Drug Metabolism and Pharmacokinetics(1991)
Abstract
Pharmacokinetic studies on time-course in the blood, tissue distribution, excretion and metabolism of CPT-11, a new anti-cancer agent, were performed in rats following a single intravenous administration of 14C-CPT-11 (PP) at a dose of 10mg/kg.1. Piperidinopiperidine, UM-1, was detected in the urine as the main metabolite originating from the side-chain part of CPT-11.2. The urinary and fecal excretions of radioactivity within 72hr after dosing were 22.6 and 77.1% after administration of 14C-CPT-11 and 41.2 and 54.5% following administration of 14C-CPT-11(PP), respectively. The metabolites from the side chain part were assumed to be excreted mainly into the urine.3. The plasma and tissue concentrations of radioactivity after dosing of 14C-CPT-11 (PP) disappeared more slowly than that after administration of 14C-CPT-11. The metabolites from the side-chain part were assumed to have higher affinity to plasma and tissues, however the specific accumulation of the metabolites derived from the side-chain part were not detected in any tissues.
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Key words
pharmacokinetics,metabolic fate,single intravenous administration,c-cpt
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