Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers

Objective. Grapefruit juice contains a number of natural substances that have the capacity to inhibit the activity of human cytochrome P450 (CYP) 3A4, CYP1A2, and p-glycoprotein. We investigated the effects of grapefruit juice on the pharmacokinetics of sertraline in healthy volunteers. Methods. Eight healthy subjects volunteered for the study after providing written informed consent to participate. The study used a crossover design with two phases separated by an interval of at least 2 weeks. The subjects ingested 250 ml of grapefruit juice or 250 ml of water 3 times daily for 5 days. On day 6, each subject was given 75 mg of sertraline with 250 ml of grapefruit juice or water. Blood samples were taken 2, 4, 6, 8, 10, 24, and 48 h later. Plasma levels of sertraline were determined by high-performance liquid chromatography. Results. Grapefruit juice increased the mean peak concentrations in plasma (C-max) of sertraline from 17.6+/-6.1 to 29.3+/-11.5 ng/ml (mean+/-SD, P = 0.003) and the mean area under the plasma sertraline concentration-time curve (AUC) from 0 to infinity of sertraline from 402.0+/-151.9 to 820.5+/-313.0 h ng/ml (mean+/-SD, P = 0.002). Conclusion. These results suggest that grapefruit juice affects the pharmacokinetics of sertraline.