Pharmacodynamic analysis of the electrocardiographic interaction between disopyramide and erythromycin in rats
作者： Erika Hanada , Hisakazu Ohtani , Hajime Kotaki , Yasufumi Sawada , Hitoshi Sato
DOI: 10.1021/JS980256R
关键词:
摘要: Disopyramide (DP) is known to induce QT prolongation and Torsades de Pointes (TdP) when administered concomitantly with erythromycin (EM). To define evaluate quantitatively the arrhythmogenic risk of concomitant administration DP EM, we investigated influence EM on pharmacokinetics pharmacodynamics in rats. The time profiles change interval plasma concentration each drug were evaluated during after constant intravenous infusion (6.0 or 15.0 mg/kg/h), (4.0 8.0 coadministration (DP 6.0 mg/kg/h plus 4.0 mg/kg/h). Each agent induced at concentrations within therapeutic range humans. DP-induced was proportional its concentration. In case Emax model an "effect compartment" could explain relationship between changes interval. Although gave enhanced compared dosing alone, did not affect DP. conclusion, it shown that a pharmacodynamic interaction contributes electrocardiographic adverse reaction (i.e., prolongation) by
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