The comparative plasma pharmacokinetics of intravenous cefpodoxime sodium and oral cefpodoxime proxetil in beagle dogs

The pharmacokinetic properties of cefpodoxime, and its prodrug, cefpodoxime proxetil, were evaluated in two separate studies, one following intravenous (i.v.) administration of cefpodoxime sodium and the second after oral (p.o.) administration of cefpodoxime proxetil to healthy dogs. After cefpodoxime administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). A single i.v. administration of cefpodoxime sodium at a dose of 10 mg cefpodoxime/kg body weight resulted in a cefpodoxime average maximum plasma concentration (C-max) of 91 (+/- 17.7) mu g/mL, measured at 0.5 h after drug administration, an average half-life (t(1/2)) of 4.67 (+/- 0.680) h, an average AUC(0-infinity) of 454 (+/- 83.1) h.mu g/mL, an average V-d(ss) of 151 (+/- 27) mL/kg, an average Cl-B of 22.7 (+/- 4.2) mL/h/kg and an average MRT0-infinity of 5.97 (+/- 0.573) h. When dose normalized to 10 mg cefpodoxime/kg body weight, cefpodoxime proxetil administered orally resulted in C-max of 17.8 +/- 11.4 mu g/mL for the tablet formulation and 20.1 +/- 6.20 mu g/mL for the suspension formulation and an average AUC(0-LOQ) of 156 (+/- 76.1) h.mu g/mL for the tablet formulation and 162 (+/- 48.6) h.mu g/mL for the suspension formulation. Relative bioavailability of the two oral formulations was 1.04 (suspension compared with tablet), whereas the absolute bioavailability of both oral formulations was estimated to be approximately 35-36% in the cross-study comparison with the i.v. pharmacokinetics. Combined with previous studies, these results suggest that a single daily oral dose of 5-10 mg cefpodoxime/kg body weight as cefpodoxime proxetil maintains plasma concentrations effective for treatment of specified skin infections in dogs.