The Metabolism of the Neuroleptic Agent 1-(4′ -Fluorophenyl)-4-(cyclohexyl-1′-piperazinyl-4′-carboxylate)-butan-1-one Hydrochloride in Rats and Man

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Abstract
1. An oral dose of the neuroleptic agent 1-(4′-fluor ophenyl)-4-(cyclohexyl-1′-[14 C]piperazinyl-4′-carboxylate)butan-1-one was mainly eliminated in the urine within 12 h by rats and man. During 5 days, 63.6% and 83.3% was eliminated in the urine of rats and man respectively. 2. Plasma concentrations in man reached a maximum during 30 min to 1 h, representing 1.43μg equiv./ml. The proportion of unchanged drug in plasma decreased from 48% at 15 min to less than 10% after 1 h. 3. Seven major radioactive components were detected in the chloroform extract of basified rat urine and five major components in similar extracts of human urine. The major rat metabolites were isolated and identified by mass spectrometry as components resulting from mono- and dihydroxylation in the cyclohexane ring, reduction of the keto group to a secondary alcohol and hydrolysis and decarboxylation of the cyclohexylcarbamoyl group. The major metabolite in the rat urine extract was the dihydroxylated secondary alcohol derivative while the major human metabolite was the monohydroxylated secondary alcohol derivative. The metabolites were also partly eliminated as conjugates.