Background: Plazomicin is a next-generation aminoglycoside (AG) with a structure that protects it from common AG resistance mechanisms in Enterobacteriaceae, and with in vitro activity against extended spectrum β-lactamase-producing and carbapenem-resistant Enterobacteriaceae. The purpose of this study was to evaluate the metabolism and excretion of plazomicin in healthy human subjects.
Methods: Six healthy male subjects were administered a single 30-minute intravenous infusion of 15 mg/kg [14C]-plazomicin (~100 µCi/dose). Following administration, blood (and plasma), urine, and feces were collected for 7 days. Total radioactivity was analyzed by liquid scintillation counting; plazomicin concentration was analyzed by a validated liquid chromatography-tandem mass spectrometry method; and metabolite profiling was conducted by accelerator mass spectrometry (AMS).
Results: The majority of the total administered radioactivity was recovered in urine (89.1%), with negligible amounts (<0.2%) excreted in feces. Radioactivity was rapidly eliminated, with ~56% of the total radioactivity recovered in urine within the first 4 hours postdose and >85% recovered in urine by 48 hours postdose. Analysis of non-radiolabeled plazomicin demonstrated that 97.5% of the dose was recovered as unchanged parent drug in urine by the end of the last sampling interval. Metabolite profiling of plasma and urine using AMS showed that [14C]-plazomicin was the only definable peak present, accounting for 94.3% and 93.6%, respectively, of the total carbon content.
Conclusion: Mass balance was achieved for 14C-labeled and for non-radiolabeled plazomicin as the majority of the administered dose was recovered in urine, with negligible amounts in the feces. Plazomicin was eliminated as unchanged drug by the kidneys and thus did not appear to be metabolized to any appreciable extent. No metabolites were detected by AMS and plazomicin was the only definable peak present in plasma and urine.
M. Sanghvi, Xceleron: Employee , Salary .
S. V. Dhuria, Achaogen, Inc.: Employee , Salary .