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Titolo:
Greater quinidine-induced QTc interval prolongation in women
Autore:
Benton, RE; Sale, M; Flockhart, DA; Woosley, RL;
Indirizzi:
Georgetown Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Georgetown Univ, Med Ctr, Dept Internal Med, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 4, volume: 67, anno: 2000,
pagine: 413 - 418
SICI:
0009-9236(200004)67:4<413:GQQIPI>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
TORSADES-DE-POINTES; SEX; PLASMA; GENDER; DIHYDROQUINIDINE; ERYTHROMYCIN; D,L-SOTALOL; MECHANISMS; DIFFERENCE; CHANNEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Woosley, RL Georgetown Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, 3900 Reservoir Rd NW, Washington, DC 20007 USA Georgetown Univ 3900 Reservoir Rd NW Washington DC USA 20007 A
Citazione:
R.E. Benton et al., "Greater quinidine-induced QTc interval prolongation in women", CLIN PHARM, 67(4), 2000, pp. 413-418

Abstract

Background: Prolongation of the electrocardiographic QT interval by drugs is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia termed torsades de pointes. Women are at greaterrisk than men for development of this adverse event when taking drugs thatprolong the QT interval, To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidine-induced QT interval lengthening inhealthy young men and women,Methods: Twelve women and 12 men received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blind, randomized crossover trial, Total plasma and protein-free concentrations of quinidine and 3-hydroxyquinidine were measured in serum, QT intervals were determined and corrected for differences in heart rate with use of the method of Bazett (QTc = QT/RR1/2),Results: As expected, the mean QTc interval at baseline was longer for women than for men (mean +/- SD; 407 +/- 7 versus 395 +/- 9 ms, P < .05), The slope of the relationship between change in the QTc interval (Delta QTc) from baseline to the serum concentration of quinidine was 44% greater for women than for men (mean +/- SE; 42.2 +/- 3.4 versus 29.3 +/- 2.6 ms/mu g per mt, P < .001), These results were not influenced by analysis of 3-hyrdroxyquinidine, free concentrations of quinidine and 3-hydroxyquinidine, or the JT interval. Conclusions: Quinidine causes greater QT prolongation in women than in menat equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced torsades de pointes observed in women taking quinidine and has implications for other cardiac and noncardiac drugs that prolong the QTc interval. Adjustment of dosages based on body size alone are unlikely to substantially reduce the increased risk of torsades de pointes in women.

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Documento generato il 23/01/20 alle ore 06:31:09