Mass Balance and Drug Interaction Potential of IV Eravacycline Administered to Healthy Subjects [Pharmacology]

Eravacycline is a novel, fully-synthetic fluorocycline that is undergoing clinical development for treating serious bacterial infections due to multidrug-resistant pathogens. We report results from three studies in healthy subjects that investigated the distribution, metabolism, and excretion of intravenous (IV) eravacycline and the effect of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) on the pharmacokinetics (PK) of IV 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 L) was greater than extracellular fluid, which suggests distribution beyond the central compartment. In the drug-drug interaction studies, mean AUC_0-t and half-life were increased approximately 30%-40% after a concomitant dose of IV eravacycline and itraconazole and clearance was decreased. A reduction in total eravacycline exposure (AUC) of approximately 25%-35% and an increase in CL of approximately 50% occurred with concomitant eravacycline and rifampin. The dose of eravacycline should be increased to 1.5 mg/kg Q12H when coadministered with a strong CYP3A inducer.

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