Effect of grapefruit juice on cabergoline pharmacokinetics in patients with Parkinson's disease

Abstract

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:

Pharmacokinetic characteristics of agents applied in the treatment of Parkinson’s disease

“…Grapefruit juice is well known to inhibit the actions of P-glycoprotein and CYP3A4. The combination of dopamine receptor agonists with grapefruit juice increases the plasma concentration of the drug [2]. The effect of grapefruit juice lasts ■ Drug-drug interactions Drug-drug interactions are a common feature in the treatment of Parkinson's disease.…”

A validated LC–MS/MS method for analysis of Cabergoline in human plasma with its implementation in a bioequivalent study: investigation of method greenness

“…Many bioequivalence studies were recorded for CAB including estimation of the effect of grapefruit juice, food, and clarithromycin on the bioavailability of CAB [ 23 – 25 ]. However, no bioequivalence studies were recorded for comparing any generic formulations for CAB and the brand product Dostinex tablets till now.…”