Comparison of the pharmacokinetics, safety and tolerability of daptomycin in healthy adult volunteers following intravenous administration by 30 min infusion or 2 min injection

Abstract

ObjectivesTwo randomized Phase I studies in separate populations of healthy adult volunteers investigated the pharmacokinetics, safety and tolerability of daptomycin (Cubicin®; Novartis Pharma AG, Basel, Switzerland) administered as a 2 min intravenous (iv) injection, relative to the currently licensed 30 min iv infusion.MethodsStudy 1 was an open-label, single-dose, two-period, crossover study in which each subject received 6 mg/kg daptomycin administered as a 30 min iv infusion (n = 15) and as a 2 min iv injection (n = 16). In Study 2, a single-blind, multiple-dose, parallel-group study, subjects received a once-daily 2 min iv injection of 6 mg/kg daptomycin (n = 12), 4 mg/kg daptomycin (n = 8) or placebo (n = 4) for 7 days. Single-dose pharmacokinetics were assessed at various timepoints up to 36 and 24 h post-dose in Study 1 and Study 2, respectively, and multiple-dose pharmacokinetics were assessed in Study 2 at day 7 for 48 h post-dose.ResultsIn Study 1, pharmacokinetic comparability between the two administration regimens was demonstrated by meeting the bioequivalence criteria for the exposure parameters, AUC0–t, AUC0–∞ and Cmax. In Study 2, time-invariant pharmacokinetic properties as well as dose-proportional pharmacokinetics were demonstrated for the daptomycin 2 min iv injection regimen. In both studies, daptomycin was well tolerated and the majority of treatment-emergent adverse events were of mild intensity and considered to be unrelated to daptomycin.ConclusionsThe similar pharmacokinetic and safety profiles of the two administration regimens suggest that the 2 min iv injection may be a convenient treatment option for both patients and healthcare professionals.