Pharmacokinetics, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects

BACKGROUND AND OBJECTIVES: Dalbavancin is a novel, once-weekly glycopeptide antibiotic approved for treatment of acute bacterial skin infections. Given the importance of understanding any pharmacokinetic variability across different patient populations, a double-blind, placebo-controlled study was conducted to evaluate the pharmacokinetics, safety, and tolerability of a single 500-mg and a single 1000-mg intravenous dose of dalbavancin in healthy Japanese subjects. METHODS: Ten subjects received intravenous dalbavancin 1000 mg, five subjects received intravenous dalbavancin 500 mg, and three subjects received intravenous placebo. RESULTS: After a single infusion of dalbavancin, the maximal plasma concentration (C(max)) and area under the plasma concentration–time curve (AUC) increased in a proportional manner from 500 mg to 1000 mg (C(max): 157 μg/ml and 299 μg/ml; AUC(last): 10,850 μg·h/ml and 22,679 μg·h/ml, on the 500-mg and 1000-mg regimens, respectively) with low inter-subject variability. The mean terminal phase half-life (t(1/2)) was 204 and 193 h after the 500-mg and 1000-mg dose, respectively. Clearance and volume of distribution were similar for the two dose concentrations. Treatment-emergent adverse events reported were considered to be of mild intensity. There were no relevant changes in laboratory values or vital signs over time in subjects in either treatment group. CONCLUSIONS: Overall, dalbavancin 500 mg and dalbavancin 1000 mg, administered as a single 30-min infusion, was well tolerated in this population and resulted in plasma exposures similar to those in non-Asians.