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

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,τ) and C_max values at baseline were 0.39 μg ml⁻¹ h and 0.14 μg ml⁻¹, respectively. During tolcapone treatment these values were on average 0.35 μg ml⁻¹ h (AUC(0,τ), week 1–2), 0.34 μg ml⁻¹ h (AUC(0,τ), week 6 and 0.13 μg 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 between tolcapone and carbidopa.

DOI: 10.1046/j.1365-2125.1999.00027.x

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