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.


METHODS
Double-blind, randomized, placebo-controlled, crossover clinical trial.


METHODS
Ambulatory academic referral center. Patients Thirteen patients with idiopathic Parkinson disease taking levodopa and experiencing motor fluctuations and dyskinesia.


METHODS
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.


METHODS
Change in finger-tapping speed, measured using the area under the curve (AUC) for finger taps per minute across time; peak finger-tapping 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 x minutes (P = .006) and more than doubled the AUC for finger-tapping speed. Pramipexole increased peak finger-tapping 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.
Brodsky
Matthew A
MA
Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, OP-32, Portland, OR 97239. brodskym@ohsu.edu.
Park
Byung S
BS
Nutt
John G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052160:Benzothiazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D018570:Risk Assessment; D016896:Treatment Outcome
D052160:Benzothiazoles; D018491:Dopamine Agonists; D007980:Levodopa; D000077487:Pramipexole