Dramatic inhibition of amiodarone metabolism induced by grapefruit juice.

Aims Grapefruit juice increases blood concentrations of many drugs metabolized by CYP3A. Amiodarone is metabolized by CYP3A to N-desethylamiodarone (N-DEA). The aim of this study was to determine amiodarone kinetics when administrated with and without grapefruit juice. Methods Eleven healthy adult volunteers took part in a single sequence, repeated-measures design study. Each subject, who had been evaluated 6 months previously for amiodarone pharmacokinetics, was given a single oral dose of amiodarone (17 mg kg -1 ) with three glasses of 300 ml of grapefruit juice on the same day. Results Grapefruit juice completely inhibited the production of N-DEA, the major metabolite of amiodarone, in all subjects and increased the area-under-the-curve (AUC) and maximum concentration of amiodarone (C max ) by 50% and 84%, respectively, as compared with the control period during which water had been administrated instead of grapefruit juice (AUC: 35.9±14.3 vs 23.9±11.2 μg ml -1 h, P<0.005 and C max : 3.45±1.7 vs 1.87±0.6 μg ml -1 , P<0.02, respectively) (means ± s.d.). This inhibition of N-IDEA production led to a decrease in the alterations caused by amiodarone on PR and QTc intervals. Conclusions Grapefruit juice dramatically alters the metabolism of amiodarone with complete inhibition of N-DEA production. These results are in agreement with in vitro data pointing to the involvement of CYP3 A in the metabolism of amiodarone and suggests that this interaction should be taken into account when prescribing this antiarrhythmic drug.