Effects of a dopamine agonist on the pharmacodynamics of levodopa in parkinson disease

Background: Treatment of Parkinson disease commonly includes levodopa and dopamine agonists; however, the interaction of these 2 drugs is poorly understood. Objective: To examine the effects of a dopamine agonist on the motor response to levodopa. Design: Double-blind, randomized, placebo-controlled, crossover clinical trial. Setting: Ambulatory academic referral center. Patients: Thirteen patients with idiopathic Parkinson disease taking levodopa and experiencing motor fluctuations and dyskinesia. Interventions: Eligible individuals were randomly assigned to receive pramipexole dihydrochloride or placebo for 4 weeks followed by a 2-hour intravenous levodopa infusion on consecutive days at 2 rates and with blinded assessments. They were then crossed over to the alternate oral therapy for 4 weeks followed by levodopa infusion and reassessment. Main Outcome Measures: Change in finger-tapping speed, measured using the area under the curve (AUC) for finger taps per minute across time; peak fingertapping speed; duration of response; time to "ON" (defined as a 10% increase in finger-tapping speed above baseline); walking speed; and dyskinesia AUC. Results: Pramipexole with levodopa infusion increased finger-tapping speed beyond the change in baseline by a mean (SE) of 170 (47.2) per minute × minutes (P=.006) and more than doubled the AUC for fingertapping speed. Pramipexole increased peak fingertapping speed by a mean (SE) of 18 (8.5) taps per minute (P=.02) and improved mean (SE) walking speed (15.9 [0.70] vs 18.9 [0.70] seconds, P=.004). Pramipexole prolonged duration of response after levodopa infusion and shortened time to ON. Pramipexole increased mean (SE) baseline dyskinesia scores (26.0 [5.85] vs 12.1 [5.85] points, P=.05) and peak dyskinesia scores with levodopa infusion. Conclusions: Pramipexole augmented the motor response to levodopa beyond a simple additive effect and increased the severity of levodopa-induced dyskinesia. When considering a combination of these therapies, an appropriate balance should be maintained regarding gain of motor function vs worsening of dyskinesia. Trial Registration: clinicaltrials.gov Identifier: NCT00666653