The effect of tolcapone on the pharmacokinetics of beserazide

This study investigated the potential interaction between tolcapone, a cate chol-O-methyltransferase (COMT) inhibitor, and the decarboxylase inhibitor, benserazide. In an open-labelled sis-week study, patients with Parkinson's disease (PD), treated with levodopa/benserazide, were given tolcapone at 2 00 mg t.i.d. Blood samples for analysis of benserazide, its main active met abolite, trihydroxybenzylhydrazine, levodopa and 3-O-methyldopa (3-OMD) wer e collected immediately before and repeatedly after the first drug intake o f the day at baseline and after 1-2 and 6 weeks of treatment. Furthermore, animal experiments were performed to determine the levels of benserazide an d trihydroxybenzylhydrazine at doses for which safety had previously been e stablished. It mas shown that tolcapone can cause an increase in benserazid e plasma concentrations and that this effect is dependent on the benserazid e dose. When tolcapone was combined with 25 mg benserazide the elevation wa s small. Although the increase was more pronounced when tolcapone was combi ned with 50 mg benserazide, the levels were still substantially lower than concentrations causing toxicity in animals. The safety margin derived from this study, together with the absence of any organic toxic effects in clini cal trials, show that the observed interaction between tolcapone and benser azide does not represent a safety concern for PD patients treated with this combination. Eur J Neurol 6:211-219 (C) 1999 Lippincott Williams & Wilkins .