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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.

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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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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.

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: