A CYP3A4 inhibitor increased the effect of cabergoline in the treatment of Parkinson's disease

Introduction Cabergoline is a synthetic ergote dopamine agonist that is metabolized by CYP3A4, is applied in the treatment of Parkinson's disease (PD). Clarithromycin, one of macrolide antibiotics, is a potent inhibitor of the CYP3A4. We studied the effect of coadministration of clarithromycin with cabergoline in healthy male volunteers and in patients with PD. Methods Trial1: Ten healthy male volunteers were enrolled. Subjects were randomized to take a single oral dose of cabergoline 1mg/day for 6 days, or a single oral dose of cabergoline plus clarithromycin 400mg/day for 6 days. Trial2: Seven patients with PD who treated with cabergoline were enrolled. They were evaluated with their symptoms of PD and blood concentration of cabergoline before and after the coadministration with clarithromycin for 6 days. Results In healthy male volunteers, the mean of Cmax and AUC of cabergoline increased around 2.7 times by coadministration of clarithromycin. In patients with PD, the blood concentration of cabergoline increased 1.73 times and three of 7 patients showed improvement in their PD sign through coadministration. Conclusion Coadministration with clarithromycin may increase the effect of cabergoline on the treatment of PD. Clinical Pharmacology & Therapeutics (2005) 77, P82–P82; doi: 10.1016/j.clpt.2004.12.204