Pharmacokinetics and Safety of Omadacycline in Subjects With Impaired Renal Function [PublishAheadOfPrint]

Many antibiotics require dosing adjustments in patients with renal impairment and/or in those undergoing hemodialysis. Omadacycline, the first aminomethylcycline antibiotic in late-stage clinical development, displays activity against a broad-spectrum of bacterial pathogens, including resistant strains. Data from completed phase 3 acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) studies showed intravenous (IV) to once-daily oral omadacycline to be clinically effective and well tolerated. To determine if dosing of omadacycline should be adjusted in patients with impaired renal function, a phase 1 study examining the pharmacokinetics (PK) and safety of IV (100 mg) omadacycline was conducted in subjects with end-stage renal disease (ESRD) on stable hemodialysis (n = 8) and in matched healthy subjects (n = 8). IV administration of omadacycline produced a similar plasma concentration-time profile in subjects with ESRD and healthy subjects. Further, in subjects with ESRD, similar PK parameters were observed when omadacycline was administered IV after or before dialysis. The mean AUC_0-inf was 10.30 h·μg/mL when administered after dialysis, 10.20 h·μg/mL before dialysis, and 9.76 h·μg/mL in healthy subjects. The mean C_max in ESRD subjects was 1.88 μg/mL when administered after dialysis and 2.33 μg/mL when administered before dialysis, and in healthy subjects was 1.92 μg/mL. The 100-mg IV dose of omadacycline was generally safe and well-tolerated in both ESRD and healthy subjects. This study demonstrates that no dose adjustment is necessary for omadacycline in patients with impaired renal function or on days when patients are receiving hemodialysis.

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