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Titolo:
Dramatic inhibition of amiodarone metabolism induced by grapefruit juice
Autore:
Libersa, CC; Brique, SA; Motte, KB; Caron, JF; Guedon-Moreau, LM; Humbert, L; Vincent, A; Devos, P; Lhermitte, MA;
Indirizzi:
Hop Cardiol, INSERM, CH&U, Clin Invest Ctr, F-59037 Lille, France Hop Cardiol Lille France F-59037 Clin Invest Ctr, F-59037 Lille, France Univ Lille 2, Fac Med, Serv Pharmacol Hosp, Unite Pharmacol Clin, F-59045 Lille, France Univ Lille 2 Lille France F-59045 Pharmacol Clin, F-59045 Lille, France Hop Calmette, Dept Biochim Toxicol, F-59037 Lille, France Hop Calmette Lille France F-59037 Biochim Toxicol, F-59037 Lille, France CHRU, Delegat Rech, F-59037 Lille, France CHRU Lille France F-59037CHRU, Delegat Rech, F-59037 Lille, France
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 4, volume: 49, anno: 2000,
pagine: 373 - 378
SICI:
0306-5251(200004)49:4<373:DIOAMI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
MECHANISM-BASED INACTIVATION; ANTIARRHYTHMIC EFFICACY; INTRAVENOUS AMIODARONE; CYTOCHROME-P450 3A4; DRUG-INTERACTIONS; ORAL AMIODARONE; N-DEETHYLATION; RAT-LIVER; DESETHYLAMIODARONE; SERUM;
Keywords:
amiodarone; grapefruit juice; interaction; metabolism; pharmacokinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Libersa, CC Hop Cardiol, INSERM, CHRU, CIC, Blvd Pr J Leclercq, F-59037 Lille, France Hop Cardiol Blvd Pr J Leclercq Lille France F-59037 e, France
Citazione:
C.C. Libersa et al., "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice", BR J CL PH, 49(4), 2000, pp. 373-378

Abstract

Aim 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 monthspreviously 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, themajor 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 vs23.9 +/- 11.2 mu g ml(-1) h, P < 0.005 and C-max: 3.45 +/- 1.7 vs 1.87 +/-0.6 mu g ml(-1), P < 0.02, respectively) (means +/- s.d.). This inhibitionof 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 intoaccount when prescribing this antiarrhythmic drug.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 16:07:32