Drug-induced QT prolongation in women during the menstrual cycle.
Autor: | Rodriguez I; Georgetown University Medical Center, 3900 Reservoir Rd NW, Med-Dent Bldg, Room SE 402, Washington, DC 20007, USA., Kilborn MJ, Liu XK, Pezzullo JC, Woosley RL |
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Jazyk: | angličtina |
Zdroj: | JAMA [JAMA] 2001 Mar 14; Vol. 285 (10), pp. 1322-6. |
DOI: | 10.1001/jama.285.10.1322 |
Abstrakt: | Context: Women have a higher incidence of torsades de pointes than men, but it is not known if the risk of drug-induced torsades de pointes varies during the menstrual cycle. Objectives: To determine if the degree of QT prolongation in response to ibutilide varies with the menstrual cycle phase and to compare QT prolongation between women and men. Design and Setting: Cohort study of men and women who received the same intervention conducted between November 1998 and November 2000 at a general clinical research center of a university hospital. Participants: A volunteer sample of 58 healthy adults (38 men and 20 women) aged 21 to 40 years. Intervention: A low dose of ibutilide (0.003 mg/kg), infused intravenously for 10 minutes. Subjects were monitored for 120 minutes. Women received the intervention on 3 separate occasions to correspond with menstrual cycle phases, which were verified by using hormonal assays. Main Outcome Measure: QT interval, recorded from electrocardiogram at timed intervals during and after ibutilide infusion and standardized for variations in heart rate (QTc). Results: Maximum (mean [SD]) millisecond increase in QTc after ibutilide infusion was greater for women during menses (63 [13]) and the ovulatory phase (59 [17]) compared with women during the luteal phase (53 [14]) and compared with men (46 [16]; P =.002 vs menses and P =.007 vs ovulation). Progesterone (r = -0.40) and progesterone-to-estradiol ratio (r = -0.41), but not estradiol (r = 0.14) or testosterone (r = 0.09), were inversely correlated with ibutilide-induced QT prolongation. Conclusions: Menstrual cycle and sex differences exist in QTc responses to ibutilide, with the greatest increase in QTc corresponding to the first half of the menstrual cycle. |
Databáze: | MEDLINE |
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