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Br J Clin Pharmacol. 2000 Apr;49(4):373-8.

Dramatic inhibition of amiodarone metabolism induced by grapefruit juice.

Author information

1
Unité de Pharmacologie Clinique, Service de Pharmacologie Hospitalière, Faculté de Médecine, Université Droit et Santé, 1 Place de Verdun, 59045 Lille Cedex, France. ciclille@chru-lille.fr

Abstract

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 (Cmax) 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 microg ml-1 h, P < 0.005 and Cmax: 3.45 +/- 1.7 vs 1.87 +/- 0.6 microg ml-1, P < 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.

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.

PMID:
10759694
PMCID:
PMC2014943
DOI:
10.1046/j.1365-2125.2000.00163.x
[Indexed for MEDLINE]
Free PMC Article

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