COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients on levodopa/carbidopa (Sinemet (R))

Aims Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor use d as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to im prove treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of c arbidopa. Methods This was an open-label study in 12 parkinsonian patients receiving optimal levodopa/carbidopa therapy and tolcapone 200 mg three times daily f or 6 weeks. Blood samples were taken at baseline (i.e. before the first tol capone intake) and after 1-2 weeks and 6 weeks so that carbidopa pharmacoki netics before and during tolcapone treatment could be assessed. Results No changes in any pharmacokinetic parameters of carbidopa were obse rved. The mean AUC(0,tau) and C-max values at baseline were 0.39 mu g ml(-1 ) h and 0.14 mu g ml(-1), respectively. During tolcapone treatment these va lues were on average 0.35 mu g ml(-1) h (AUC(0,tau), week 1-2), 0.31 mu g m l(-1) h (AUC(0,tau), week 6 and 0.13 mu g ml(-1) (C-max, weeks 1-2 and 6). t(max) 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 betwe en tolcapone and carbidopa.