Abstract. Cabergoline is used in the treatment of Parkinson's disease (PD). Clarithromycin is a potent inhibitor of CYP3A4 and P-glycoprotein and is often co-administered with cabergoline in usual clinical practice. We studied the effect of clarithromycin co-administration on the blood concentration of cabergoline in healthy male volunteers and in PD patients. Study 1: Ten healthy male volunteers were enrolled and were randomized to take a single oral dose of cabergoline (1 mg / day) for 6 days or a single oral dose of cabergoline plus clarithromycin (400 mg / day) for 6 days. Study 2: Seven PD patients receiving stable cabergoline doses were enrolled. They were evaluated for the plasma cabergoline concentration before and after the addition of clarithromycin 400 mg / day for 6 days, and again 1 month after discontinuation of clarithromycin. The dose and duration of clarithromycin were decided according to usual clinical practice. In healthy male volunteers, mean C max and AUC 0-10 h of cabergoline increased to a similar degree during coadministration of clarithromycin. Mean plasma cabergoline concentration over 10 h post-dosing increased 2.6-fold with clarithromycin co-administration. In PD patients, plasma cabergoline concentration increased 1.7-fold during clarithromycin co-administration. Co-administration with clarithromycin may increase the blood concentration of cabergoline in healthy volunteers and in PD patients.
Background
Cabergoline is one of the synthetic ergoline dopamine agonists, which is widely used for the treatment of Parkinson's disease (PD). Cytochrome P‐450 (CYP) 3A4 contributes to metabolize Cabergoline. It has been well known that grapefruit juice inhibits CYP3A4 enzyme located in the gut wall. To investigate whether grapefruit juice influences the pharmacokinetics of cabergoline, plasma level of cabergoline in patients of PD was evaluated.
Methods
Five patients with PD treated with cabergoline were enrolled. Plasma concentrations of cabergoline before and after coadministration of grapefruit juice were evaluated. The plasma concentration of cabergoline was determined using a LC/MS/MS.
Results
The plasma concentration of cabergoline increased approximately 1.7 times, when grapefruit juice was taken together with cabergoline. Adverse events were not observed during this trial.
Conclusions
Coadministration of grapefruit juice with cabergoline increases bioavailability of cabergoline. A relatively large therapeutic window of cabergoline may allow the concomitant treatment with grapefruit juice, and this combination treatment may augment the antiparkisonian effect of cabergoline.
Clinical Pharmacology & Therapeutics (2005) 77, P84–P84; doi:
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