End-of-dose akinesia after a single intravenous infusion of the dopaminergic agonist piribedil in Parkinson's disease patients: a pharmacokinetic/pharmacodynamic, randomized, double-blind study.
This randomized, double-blind trial was designed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from off to on state after single intravenous infusion. Ten fluctuating patients with idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2-16 mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the motor deficit (UPDRS, motor score) including akinesia at the first evaluation time point of 15 minutes, and in reversing off state of 7 of 10 patients. The doses were equally effective, although the effect was more sustained with the highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil were not correlated to the motor score improvement or switch from off-->on. In conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and effective in improving motor symptoms, including akinesia, of fluctuating PD patients.
Simon
Nicolas
N
Laboratoire de Pharmacologie Medicale et Clinique, Centre Hospitalier Universitaire Timone, Marseille, France.
Micallef
Joëlle
J
Reynier
Jean-Charles
JC
Lesourd
Monique
M
Witjas
Tatiana
T
Alicherif
André
A
Azulay
Jean-Philippe
JP
Blin
Olivier
O
D000368:Aged; D018491:Dopamine Agonists / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000379:methods; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy*; D010891:Piribedil / Q000097:blood / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D018491:Dopamine Agonists; D010891:Piribedil