Red wine-cisapride interaction: Comparison with grapefruit juice

Objectives Our objective was to compare the interactions of red wine and grapefruit juice with cisapride. Methods The oral pharmacokinetics of cisapride, its norcisapride metabolite, and electrocardiographic QTc interval were determined over a 24‐hour period after administration of cisapride 10 mg with 250 mL grapefruit juice, red wine (cabernet sauvignon), or water in a randomized 3‐way crossover study in 12 healthy men. Results The cisapride area under the concentration‐time curve (AUC) and the maximum plasma drug concentration after single‐dose administration (Cmax) with grapefruit juice were 151% (P < .01) and 168% (P < .001), respectively, of those with water. The increase in cisapride AUC and Cmax was variable among individuals; however, cisapride AUC and Cmax were enhanced by the same proportion. The time to reach maximum concentration after drug administration (tmax) and the apparent elimination half‐life (t½ for cisapride and the pharmacokinetics of norcisapride were not altered. Norcisapride/cisapride ratios were reduced. Cisapride AUC and Cmax with red wine were 115% (difference not statistically significant) and 107% (difference not statistically significant), respectively, of those with water. The cisapride tmax was slightly longer. Cisapride t½ and norcisapride pharmacokinetics were not different. The norcisapride/cisapride ratio at cisapride Cmax was lower. One subject had a doubling in cisapride AUC and Cmax and a decrease in norcisapride/cisapride ratios with red wine and also had the largest interaction with grapefruit juice. QTc interval was unchanged in all treatment groups and individuals. Conclusions A single glass of grapefruit juice produced an individual‐dependent variable increase in the systemic availability of cisapride by inhibition of intestinal cytochrome P450 3A4 (CYP3A4) activity. The identical volume of red wine caused only minor changes in cisapride pharmacokinetics despite some inhibition of CYP3A4 in most individuals. However, even this amount of red wine may cause a marked interaction similar to that for grapefruit juice in individuals with a preexisting high intestinal CYP3A4 content. Clinical Pharmacology & Therapeutics (2001) 70, 17–23; doi: 10.1067/mcp.2001.116892