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• W1485654772 abstract "Aims To investigate the rate of excretion and routes of metabolism of tolcapone, a novel inhibitor of catechol-O-methyltransferase (COMT). Methods Six healthy male volunteers were given 200 mg [14C]-tolcapone (approximately 50 μCi) orally. To assess excretion balance and to identify metabolites, urine and faeces were collected before administration and until radioactivity fell below 75 d min−1 ml−1 (urine) and 100 d min−1 mg−1 (faeces). Blood samples were collected frequently before and after administration to determine plasma radioactivity, to identify tolcapone metabolites and to measure plasma tolcapone and its methylated derivative 3-O-methyltolcapone (3-OMT). Results The mean proportion of the dose excreted in urine was 57.3% and in faeces 40.5%. Excretion was almost complete (more than 95%) in all participants after 9 days. The major early metabolite present in plasma was the 3-O-β,d-glucuronide conjugate, which was detectable within 2 h after dosing. The major late metabolite in plasma was 3-OMT. The 3-O-β,d-glucuronide was also the most abundant metabolite in urine and faeces, accounting for 27% and 33%, respectively, of the total radioactivity excreted by these routes and for 26% of the original dose. Reduction of the nitro moiety yields an amine derivative, detected in both urine and faeces, with subsequent modifications, such as acetylation of the amine group and conjugation with glucuronic acid or sulphate, or both. Oxidative reactions due to cytochrome P450 enzymes are of small significance, as is 3-O-methylation by COMT. Conclusions Tolcapone is almost completely metabolized and excreted in urine and faeces (only 0.5% of tolcapone was excreted unchanged); glucuronidation is the most important route of metabolism. The relatively long duration of excretion is caused by the long half-life of 3-OMT." @default.
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• W1485654772 date "1999-10-01" @default.
• W1485654772 modified "2023-10-14" @default.
• W1485654772 title "Metabolism and excretion of tolcapone, a novel inhibitor of catechol-<i>O</i> -methyltransferase" @default.
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• W1485654772 doi "https://doi.org/10.1046/j.1365-2125.1999.00036.x" @default.
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