Abstract

Simplicef® (cefpodoxime proxetil) is a time-dependent, oral, semi-synthetic, third generation cephalosporin, formulated for once daily dosing and FDA-approved in dogs. Simplicef® has a broad spectrum of activity that includes gram-positive and gram-negative species. Given the very few antimicrobial pharmacokinetic studies in dolphins, and paucity of once daily oral antibiotic options in this species, a population pharmacokinetic study was performed.

This study utilized a sparse-sampling design with banked and opportunistically collected serum from bottlenose dolphins (Tursiops truncatus) receiving Simplicef® at 10 mg/kg orally every 24 hours. Serum samples (n=57) from 23 dolphins were analyzed at 12 time points from 0 to 96 hours post-dose. Age and weight ranged from 2 to 46 years and 182 to 254 kg. Zoetis analyzed serum using liquid chromatography mass spectrometry and performed population pharmacokinetic analysis using nonlinear mixed-effects modeling. One- and two-compartment linear models were tested with first order absorption. Covariates including weight, age, and sex were considered for inclusion in the model, and between subject variability was incorporated; a one-compartment model performed best. The model predicted that following an oral dose of 10 mg/kg, Simplicef® plasma concentration reached a mean maximum concentration (C_max) of 13.9 µg/mL, mean time to maximum concentration (T_max) of 4.8 hours, and mean half-life (T_1/2) of 10.3 hours. With daily dosing, accumulation was approximately 30%, and steady state was reached by the third dose. Based on this data, once daily oral dosing (10 mg/kg) of Simplicef® in dolphins was well-absorbed and appears to be a safe, effective option for susceptible bacterial isolates.

Acknowledgements

The authors thank the veterinary technicians, especially Melinda Martens, Katie Hodges, Jenny Kane, Jammy Eichman, and Joy Middleton, as well as the medical records office and training staff at the National Marine Mammal Foundation and U.S. Navy Marine Mammal Program for their excellent care of the U.S. Navy’s marine mammals.

*Presenting author