We investigated whether administration of the catechol-O-methyl transferase 
(COMT) inhibitor entacapone, at doses of 200 mg and 400 mg, alters the 
pharmacokinetics of apomorphine in Parkinson's disease patients experiencing 
severe motor fluctuations. In addition, the pharmacodynamics and safety of 
entacapone and apomorphine coadministration in these patients were examined. The 
study followed a three-sequence, three-period, crossover design. Patients were 
randomly assigned to one of three sequences that included single oral doses of 
entacapone 200 mg, entacapone 400 mg, and placebo in a predefined order. On 3 
separate test days, study treatment was administered before apomorphine. The 
study evaluations (pharmacokinetics, tapping test, and dyskinesia evaluation 
[Abnormal Involuntary Movements Scale - AIMS]) were performed on these days. 
Furthermore, Unified Parkinson Disease Rating Scale (UPDRS) scores were 
evaluated at baseline and study end. Pharmacokinetic parameters for apomorphine 
(C(max), AUC, t(max), t(1/2)) were unchanged by the administration of 
entacapone, and changes in both the tapping test and AIMS score were similar 
with all treatments (entacapone 200 mg, entacapone 400 mg, and placebo). There 
was no significant difference in mean total UPDRS scores between baseline and 
study end. The administration of entacapone did not change the pharmacokinetic 
or pharmacodynamic effects of apomorphine in these patients or prolong the 
clinical effect of apomorphine. Thus, apomorphine may be safely administered to 
patients receiving therapy with levodopa and entacapone, providing a useful 
addition to treatment for patients with advanced Parkinson's disease.