Assessment of QT interval prolongation in combined use of NM394, an active metabolite of prulifloxacin, and erythromycin

Quinolone and macrolide antibiotics are frequently used together for acute exacerbation of chronic bronchitis. Both antibiotics show QT interval prolongation, but there is no information on their combined use. So, we evaluated NM394 (NM) and erythromycin (EM) in combination on QT interval using in vitro and in vivo models. In guinea pig papillary muscles, NM (100-1000 μM) and EM (20-200 μM) that are 30-100 times higher than therapeutic plasma levels increased action potential duration (APD) dose-dependently. This combination showed additive effect on APD. In dogs, intravenous infusion of NM and EM each at 1 mg/kg/min increased ventricular monophasic action potential duration (MAPD) at a supratherapeutic plasma level (40 μg/mL) that is 20-40 times higher than Cmax at their therapeutic doses. Both drugs in combination showed additive effect on MAPD. According to the results, each NM and EM prolonged QT interval only at the supratherapeutic dose and their combined use shows additive effect, suggesting this combination should he safe in clinical sites.