The pharmacokinetic and clinical effects of tolcapone on a single dose of sublingual apomorphine in Parkinson's disease

Apomorphine (APO) is a potent dopamine agonist that is partially metabolize d by catachol-O-methyl transferase (COMT). Tolcapone was the first COMT inh ibitor available for use as adjunctive therapy to levodopa in Parkinson's d isease (PD). In order to determine whether this compound might increase the serum area under the curve (AUC) of APO and whether this results in any cl inical benefit, we administered 200 mg doses of tolcapone to five fluctuati ng PD patients taking an investigational sublingual APO preparation. Serial tapping speed and gait speed were assessed at 15 min intervals over four h ours, in conjunction with APO serum levels, following a single dose of APO, both before and five days after starting tolcapone (600 mg/day). Serum APO levels tended to be higher (12.6%), and clinical measures suggested improv ement during the APO "on" period after the addition of tolcapone (22.5% imp rovement in gait speed, and 7.6% improvement in tapping speed), but neither . reached statistical significance. Further trials, involving larger sample s are needed to clearly establish the pharmacokinetic and clinical effect o f tolcapone in PD patients taking APO. (C) 2000 Elsevier Science Ltd. All r ights reserved.