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Titolo:
GRAPEFRUIT JUICE ALTERS TERFENADINE PHARMACOKINETICS RESULTING IN PROLONGATION OF REPOLARIZATION ON THE ELECTROCARDIOGRAM
Autore:
BENTON RE; HONIG PK; ZAMANI K; CANTILENA LR; WOOSLEY RL;
Indirizzi:
GEORGETOWN UNIV,COLL MED,DEPT PHARMACOL,3900 RESERVOIR RD NW WASHINGTON DC 20007 GEORGETOWN UNIV,MED CTR,DEPT INTERNAL MED,DIV CLIN PHARMACOL WASHINGTON DC 20007 UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARMACOL BETHESDA MD 20814
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 4, volume: 59, anno: 1996,
pagine: 383 - 388
SICI:
0009-9236(1996)59:4<383:GJATPR>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; FELODIPINE; METABOLISM; INHIBITION; FLAVONOIDS; MECHANISM; OXIDATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
R.E. Benton et al., "GRAPEFRUIT JUICE ALTERS TERFENADINE PHARMACOKINETICS RESULTING IN PROLONGATION OF REPOLARIZATION ON THE ELECTROCARDIOGRAM", Clinical pharmacology and therapeutics, 59(4), 1996, pp. 383-388

Abstract

Objectives: To establish whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by concomitant administration of grapefruit juice and to determine whether any effectof grapefruit juice is dependent on the timing of administration in relation to the dose of terfenadine. Methods: Twelve healthy volunteerswere studied in a prospective randomized trial, The primary end points were QT prolongation on the surface electrocardiogram and the pharmacokinetic parameters: area under the concentration-time curve (AUC), maximum concentration, and time to maximum concentration of terfenadineand its acid metabolite terfenadine carboxylate. All subjects received 60 mg terfenadine twice a day with 240 ml water for 7 days, They were then randomized to drink 240 ml of double-strength grapefruit juice simultaneously with terfenadine (simultaneous group) for an additional7 days or to drink the same dose of grapefruit juice 2 hours after terfenadine for 7 days (delayed group), Twelve timed electrocardiograms and plasma terfenadine and metabolite levels were measured on days 7 and 14, Results: None of the 12 subjects had quantifiable levels of terfenadine when the drug was administered with water, All six subjects who took terfenadine and drank grapefruit juice simultaneously had quanti fiable terfenadine levels, Only two of six who drank grapefruit juice 2 hours after terfenadine had quantifiable levels, The AUC of the acid metabolite increased 55% (p < 0.05) in the simultaneous group and 22% (p = NS) in the delayed group, The mean QT interval increased from420 to 434 msec (p < 0.05) in the simultaneous group and decreased from 408 to 407 msec (p = NS) in the delayed group. Conclusions: Administration of grapefruit juice concomitantly with terfenadine may lead toan increase in systemic terfenadine bioavailability and result in increases in QT interval, The clinical significance of an increase in QT interval of this magnitude is unclear.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 10:52:25