Dramatic inhibition of amiodarone metabolism induced by grapefruit juice

<jats:p><jats:bold>Aims </jats:bold> Grapefruit juice increases blood concentrations of many drugs metabolized by CYP3A. Amiodarone is metabolized by CYP3A to <jats:italic>N</jats:italic>‐desethylamiodarone (N‐DEA). The aim of this study was to determine amiodarone kinetics when administrated with and without grapefruit juice.</jats:p><jats:p><jats:bold>Methods </jats:bold> 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<jats:sup>−1</jats:sup>) with three glasses of 300 ml of grapefruit juice on the same day.</jats:p><jats:p><jats:bold>Results </jats:bold> 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 (<jats:italic>C</jats:italic><jats:sub>max</jats:sub>) 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 <jats:italic>vs</jats:italic> 23.9 ± 11.2 µg ml<jats:sup>−1</jats:sup> h, <jats:italic>P</jats:italic> < 0.005 and <jats:italic>C</jats:italic><jats:sub>max</jats:sub>: 3.45 ± 1.7 <jats:italic>vs</jats:italic> 1.87 ± 0.6 µg ml<jats:sup>−1</jats:sup>, <jats:italic>P</jats:italic> < 0. 02, respectively) (means ± s.d.). This inhibition of N‐DEA production led to a decrease in the alterations caused by amiodarone on PR and QTc intervals.</jats:p><jats:p><jats:bold>Conclusions </jats:bold> Grapefruit juice dramatically alters the metabolism of amiodarone with complete inhibition of N‐DEA production. These results are in agreement with <jats:italic>in vitro</jats:italic> 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.</jats:p>