Background: Certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. These effects may be mediated by interactions with enzyme systems, such as cytochrome P450, or with active transporter systems, such as P-glycoprotein and organic anion transporting polypeptides.
Objective: To assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine.
Design: Non-blinded, randomised, single-dose, four-way crossover study.
Participants: Twenty-four healthy adult volunteers.
Interventions: Single oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with grapefruit juice (pretreatment with 240ml of double-strength juice three times daily for 2 days prior to administration of study drug, plus the same amount simultaneously with, and 2 hours after, the drug dose). Each treatment was separated by at least 10 days.
Main outcome measures: Log-transformed pharmacokinetic parameters [peak plasma concentration (C(max)) and area under the curve (AUC)], time to maximum concentration, elimination half-life and electrocardiographic (ECG) parameters.
Results: Comparing the ratio of the pharmacokinetic parameter means (C(max) and AUC) with and without grapefruit juice (expressed as a percentage), the rate (C(max)) and extent (AUC) of absorption of fexofenadine were reduced by 30% by consumption of grapefruit juice. In contrast, the bioavailability of desloratadine was unaffected by grapefruit juice. No clinically significant changes in ECG parameters were observed following coadministration of grapefruit juice with desloratadine or fexofenadine compared with either antihistamine given alone.
Conclusion: The bioavailability of drugs that do not undergo significant intestinal or hepatic metabolism, such as fexofenadine, may be altered when administered with agents that influence drug transport mechanisms.