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  • Title: COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients in levodopa/carbidopa (Sinemet).
    Author: Jorga KM, Nicholl DJ.
    Journal: Br J Clin Pharmacol; 1999 Sep; 48(3):449-52. PubMed ID: 10510160.
    Abstract:
    AIMS: Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa. METHODS: This was an open-label study in 12 parkinsonian patients receiving optimal levodopa/carbidopa therapy and tolcapone 200 mg three times daily for 6 weeks. Blood samples were taken at baseline (i.e. before the first tolcapone intake) and after 1-2 weeks and 6 weeks so that carbidopa pharmacokinetics before and during tolcapone treatment could be assessed. RESULTS: No changes in any pharmacokinetic parameters of carbidopa were observed. The mean AUC(0,tau) and Cmax values at baseline were 0.39 microg ml-1 h and 0. 14 microg ml-1, respectively. During tolcapone treatment these values were on average 0.35 microg ml-1 h (AUC(0,tau), week 1-2), 0. 34 microg ml-1 h (AUC(0,tau), week 6 and 0.13 microg ml-1 (Cmax, weeks 1-2 and 6). tmax remained unchanged (approx. 2 h). CONCLUSIONS: These results indicate that tolcapone does not affect carbidopa elimination and that no interaction of any clinical relevance occurs between tolcapone and carbidopa.
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