Pharmacokinetic interaction between linezolid and grapefruit juice in healthy volunteers

M Cuciureanu2, R Cuciureanu1, D Munteanu3, FS Radulescu4, C Diaconu5, L Vlase3. 1University of Medicine and Pharmacy, Iasi, Environmental and Food Chemistry, Romania, 2University of Medicine and Pharmacy, Iasi, Pharmacology, Romania, 3Faculty of Pharmacy, Cluj, Pharmaceutical Technology and Biopharmaceutics, Romania, 4Facultaty of Pharmacy, Bucharest, Department of Pharmaceutical Biosciences, Romania, 5Facultaty of Pharmacy, Galati, Department of Pharmaceutical Biosciences, Romania

Introduction: Grapefruit juice inhibits the activity of CYP3A4 enzyme, P-glycoprotein and organic anion transporting polypeptides thereby modifying the bioavailability of orally co-administrated drugs. Patients: In a pilot, open label, randomized, single-dose, two-periods, crossover study with a wash-out interval of one week, 6 healthy volunteers received orally 600-mg of linezolid administrated 2 hours after 250 ml fresh red grapefruit juice (test) or respectively 250 ml water (reference) under fasting conditions. Plasma concentrations of linezolid were determined over 24 hours after drug administration using a pre-validated LC/MS/MS method. Results: For the test and reference formulation, mean C(max) values were 13830.38 ng/ml and 10406.89 ng/ml, respectively. The mean AUC(0-t) were 118435 ng x h/ml for the test and 98350.15 ng x h/ml for the reference formulation, respectively. Mean ratio (test/reference) of C(max) was 1.32 with 90% CI of 1.18 to 1.47, and of AUC(0-t) was 1.205 with 90% CI of 1.05 to 1.36. Conclusion: Our data showed the pharmacokinetic interaction between linezolid and grapefruit juice, and suggest that the observed interaction might be clinically significant, but its relevance has to be confirmed.