Red wine-cisapride interaction: Comparison with grapefruit juice

Objectives. Our objective was to compare the interactions of red wine and g rapefruit juice with cisapride. Methods. The oral pharmacokinetics of cisapride, its norcisapride metabolit e, and electrocardiographic QTc interval were determined over a 24-hour per iod after administration of cisapride 10 mg with 250 mL grapefruit juice, r ed wine (cabernet sauvignon), or water in a randomized 3-way crossover stud y in 12 healthy men. Results. The cisapride area tinder the concentration-time curve (AUC) and t he maximum plasma drug concentration after single-dose administration (C-ma x) with grapefruit juice were 151% (P < .01) and 168% (P < .001), respectiv ely, of those with water. The increase in cisapride AUC and C-max was varia ble among individuals; however, cisapride AUC and C-max were enhanced by th e same proportion. The time to reach maximum concentration after drug admin istration (t(max)) and the apparent elimination half-life (t(1/2) for cisap ride and the pharmacokinetics of norcisapride were not altered. Norcisaprid e/cisapride ratios were reduced. Cisapride AUC and C-max with red wine were 115% (difference not statistically significant) and 107% (difference not s tatistically significant), respectively, of those with water. The cisapride tmax was slightly longer. Cisapride t(1/2) and norcisapride pharmacokineti cs were not different. The norcisapridc/cisapride ratio at cisapride C-max was lower. One subject had a doubling in cisapride AUC and C-max and a decr ease in norcisapride/cisapride ratios with red wine and also had the larges t interaction with grapefruit juice. QTc interval was unchanged in all trea tment groups and individuals. Conclusions. A single glass of grapefruit juice produced an individual-depe ndent variable increase in the systemic availability of cisapride by inhibi tion of intestinal cytochrome P450 3A4 (CYP3A4) activity. The identical vol ume of red wine caused only minor changes in cisapride pharmacokinetics des pite some inhibition of CYP3A4 in most individuals. However, even this amou nt of red wine may cause a marked interaction similar to that for grapefrui t juice in individuals with a preexisting high intestinal CYP3A4 content.