Pharmacokinetic study on the interaction between cabergoline and clarithromycin in healthy volunteers and patients with parkinson's disease

Abstract

Pharmacokinetic interaction between cabergoline, a dopamine receptor agonist and a macrolide, clarithromycin was studied in healthy volunteers and patients with Parkinson's disease. Ten healthy volunteers with the age between 23 to 50 years were employed in an open, two periods, crossover study for the pharmacokinetics of cabergoline. Cabergoline was administered at the dose of 1 mg per day for 6 days with or without clarithromycin at the dose of 400 mg per days. The blood was sampled on the day 1 and on the day 6. Domperidone, a antiemetic agent was given at the dose of 10 mg with cabergoline. Coadministration of clarithromycin increased the Cmax from 55.4 to 152.9 pg/ml, and the AUC from 482 to 1268 pg/ml hr. Coadministration of clarithromycin increased bioavalability of cabergoline 2.8 times as high as clarithromycin alone. Administration of clarithromycin on patients with Parkinson's disease also increased the bioavalabitity of cabergoline 2-4 times as high as cabergoline alone. The metabolism of cabergoline through CYP3A4 would be suppressed by clarithromycin. Clarithromycin was an antibiotics applied to upper airway or skin infectious disorders. Coadministration of clarithromycin or other CYP3A4 inhibiting agents may increased the bioavalability of ergot alkaloid dopamine receptor agonists, and increased the antiparkinsonian effect of agents in patients with Parkinson's disease.