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.