Eravacycline is a novel, fully synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, including multidrug-resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (i.v.) eravacycline were evaluated in single- and multiple-ascending-dose studies. Healthy subjects received single i.v. doses of 0.1 to 3 mg/kg of body weight or 10 days of treatment with 0.5 or 1.5 mg/kg every 24 h (q24h) over 30 min, 1.5 mg/kg q24h over 60 min, or 1 mg/kg q12h over 60 min. After single doses, total exposure (the area under the plasma concentration-time curve [AUC]) and the maximum plasma concentrations (C max) of eravacycline increased in an approximately dose-proportional manner. After multiple doses, steady state was achieved within 5 to 7 days. Accumulation ranged from approximately 7% to 38% with the q24h dosing regimens and was 45% with 1 mg/kg q12h. Eravacycline was generally well tolerated, with dose-related nausea, infusion site effects, and superficial phlebitis that were mild or moderate occurring. These results provide support for the 1-mg/kg q12h regimen used in clinical studies of eravacycline.
Keywords: eravacycline; pharmacokinetics.
Copyright © 2018 Newman et al.