Abstract
Eravacycline is a novel, fully synthetic fluorocycline that is approved for the treatment of complicated intra-abdominal infections (cIAI) in adult patients. We report results from three studies in healthy subjects that investigated the distribution, metabolism, and excretion of intravenous (i.v.) eravacycline and the effect of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) on the pharmacokinetics (PK) of i.v. eravacycline. In the mass balance study, the majority of total radioactivity from [14C]eravacycline was recovered in the feces, suggesting biliary/fecal elimination is the major route of excretion for eravacycline and its metabolites after IV administration. The volume of distribution (217 liters) was greater than that of extracellular fluid, which suggests distribution beyond the central compartment. In the drug-drug interaction studies, mean area under the concentration-time curve from 0 h to the last time point (AUC0-t ) and half-life were increased approximately 30% to 40% after a concomitant dose of i.v. eravacycline and itraconazole and clearance (CL) was decreased. A reduction in total eravacycline exposure (AUC) of approximately 25% to 35% and an increase in CL of approximately 50% occurred with concomitant eravacycline and rifampin treatment. The dose of eravacycline should be increased to 1.5 mg/kg of body weight every 12 h when coadministered with a strong CYP3A inducer.
Highlights
Eravacycline is a novel, fully synthetic fluorocycline that is approved for the treatment of complicated intra-abdominal infections in adult patients
Eravacycline is highly active against both hospital- and communityacquired methicillin-susceptible or methicillin-resistant Staphylococcus aureus strains, vancomycin-susceptible or vancomycin-resistant Enterococcus faecium and Enterococcus faecalis, and penicillin-susceptible or penicillin-resistant isolates of Streptococcus pneumoniae
We report results from three studies in healthy subjects that investigated the ADME of i.v. eravacycline and the effect of a CYP3A4 inhibitor and inducer on the PK of i.v. eravacycline
Summary
Eravacycline is a novel, fully synthetic fluorocycline that is approved for the treatment of complicated intra-abdominal infections (cIAI) in adult patients. In healthy volunteers given i.v. eravacycline at 1 mg/kg q12h for 10 days, the mean peak plasma concentration (Cmax) and area under the concentration-time curve from 0 to 12 h (AUC0–12) were 1,825 ng/ml and 6,309 ng·h/ml, while volume of distribution at steady state (Vss) and clearance (CL) were 4.0 liters/kg and 0.16 liters/h/kg [3]. These values are consistent with other results from pharmacokinetic studies of i.v. eravacy-. In double-blind, randomized clinical studies, i.v. eravacycline treatment demonstrated efficacy and tolerability in patients with cIAI [7, 8]
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