Pharmacokinetics, Distribution, Metabolism, and Excretion of Omadacycline Following a Single Intravenous or Oral Dose of 14C-omadacycline in Rats [PublishAheadOfPrint]

The absorption, distribution, metabolism, and excretion of omadacycline, a first in class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, were evaluated in rats. Tissue distribution was investigated by quantitative whole-body autoradiography in male Long Evans Hooded (LEH) rats. Following a 5 mg/kg intravenous (IV) dose, radioactivity widely and rapidly distributed into most tissues. The highest tissue-to-blood ratio was observed in bone mineral, thyroid gland, and harderian gland at 24 h post IV dose. There was no evidence of stable accumulation in uveal tract tissue suggesting no stable binding interaction with melanin. Following a 90 mg/kg oral dose in LEH rats, the highest tissue-to-blood ratios (t/b) were observed in bone mineral, harderian gland, liver, spleen, and salivary gland. Plasma protein binding was 26% in the rat and 15% - 21% in other species. Omadacycline plasma clearance was 1.2 L/h/kg and half-life was 4.6 h; steady-state volume of distribution (Vss) was 6.89 L/kg. Major circulating components in plasma were intact omadacycline and its epimer. Consistent with observations in human, approximately 80% of the dose was excreted into the feces as unchanged omadacycline after IV administration. Fecal excretion was primarily the result of biliary excretion (~40%) and direct gastrointestinal secretion (~30%). However, urinary excretion (~30%) was equally prominent after IV dosing.

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