Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram*

Abstract

Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in systemic terfenadine bioavailability and result in increases in QT interval. The clinical significance of an increase in QT interval of this magnitude is unclear.

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

“…High levels of unmetabolized terfenadine are associated with significant cardiotoxicity such as QT prolongation and torsade de pointes (Woosley et al, 1993). Administration of grapefruit juice concurrently with terfenadine significantly elevated terfenadine plasma concentrations (Benton et al, 1996;Clifford et al, 1997). One glass of regular strength grapefruit juice was enough to produce maximum effect on terfenadine pharmacokinetics (Rau et al, 1997).…”

“…One glass of regular strength grapefruit juice was enough to produce maximum effect on terfenadine pharmacokinetics (Rau et al, 1997). As for cardiac effects, repeated consumptions of grapefruit juice simultaneously to 60 mg terfenadine twice a day for a week resulted in a significant increase in QT interval (Benton et al, 1996;Honig et al, 1996).…”

Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect

“…Grapefruit juice increases the oral availability of a variety of clinically used drugs that are metabolized primarily by CYP3A4 (Ducharme et al, 1995;Kupferschmidt et al, 1995;Benton et al, 1996;Bailey et al, 1998Bailey et al, , 2000. Bergamottin (BG) and 6Ј,7Ј-dihydroxybergamottin (DHBG), the two most abundant furanocoumarins present in grapefruit, have been characterized as reversible inhibitors and as mechanism-based inactivators of CYP3A4 (Schmiedlin-Ren et al, 1997;He et al, 1998;Guo et al, 2000;Ohnishi et al, 2000;Tassaneeyakul et al, 2000).…”

Interactions of medicines with dietic supplementsa

“…A similar reaction takes place with metals such as iron and copper [3]. At the end of the 1980s, there were noticed deaths due to ventricular arrhythmias in patients who used terfenadine and consumed grapefruit juice [4]. Due to the discovery that grapefruit juice contains components interfering with enzymes from the cytochrome P450 and other liver enzymes responsible for metabolizing almost 50% of drugs, interactions between food and medicines have attracted public attention, which has prompted a number of researches on the eff ect of food on drug metabolism [5,6].…”