Juvenile toxicity study of faropenem medoxomil in beagle puppies

We determined the toxicity of faropenem medoxomil (FPM) in neonatal/juvenile dogs following 28 days of administration. The puppies received vehicle or FPM beginning on Postnatal Day (PND) 22 at respective dose levels of 0, 100, 300, 600, or 1400 mg/kg-d (four daily doses (QID) of 25, 75, 150, or 350 mg/kg/dose), respectively, at a dose volume of 5 mL/kg/dose. Body weight, food consumption, clinical observation, clinical pathology, urine analysis and TK were evaluated. Body weight in males and kidney findings at 1400 mg/kg-d were considered adverse. Comparison of Day 27 TK values with Day 1 parameters showed a change in FPM pharmacokinetic behavior over time with an apparent increase in the rate of clearance characterized by a decrease in AUC(0-6) and T(max) values on Day 27 with little to no change in C(max) values. Based on these results, the No Observed Adverse Effect Level was 600 mg/kg-d.