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 metabolized by catachol-O-methyl transferase (COMT). Tolcapone was the first COMT inhibitor available for use as adjunctive therapy to levodopa in Parkinson's disease (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 clinical benefit, we administered 200 mg doses of tolcapone to five fluctuating PD patients taking an investigational sublingual APO preparation. Serial tapping speed and gait speed were assessed at 15 min intervals over four hours, 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 improvement during the APO “on” period after the addition of tolcapone (22.5% improvement in gait speed, and 7.6% improvement in tapping speed), but neither reached statistical significance. Further trials, involving larger samples are needed to clearly establish the pharmacokinetic and clinical effect of tolcapone in PD patients taking APO.