The pharmacokinetics of cefadroxil over a range of oral doses and animal ages in the foal.

Abstract

To evaluate the effect of foal age on the pharmacokinetics of cefadroxil, five foals were administered cefadroxil in a single intravenous dose (5 mg/kg) and a single oral dose (10 or 20 mg/kg) at ages of 0.5, 1, 2, 3 and 5 months. Pharmacokinetic parameters of terminal elimination rate constant (beta(po)), oral mean residence time (MRTpo), mean absorption time (MAT), rate constant for oral absorption (Ka), bioavailability F, peak serum concentrations (Cmax) and time of peak concentration (tmax), were evaluated in a repeated measures analysis over dose. Across animal ages, parameters for the intravenous dose did not change significantly over animal age (P > or = 0.05). Mean values +/- SEM were: beta(IV) = 0.633 +/- 0.038 h-1; Cl = 0.316 +/- 0.010 L/kg/h; Vc = 0.196 +/- 0.008 L/kg; Varea = 0.526 +/- 0.024 L/kg; VSS = 0.374 +/- 0.014 L/kg; MRTiv = 1.22 +/- 0.07 h; Kel = 1.67 +/- 0.08 h-1. Following oral administration, drug absorption became faster with age (P < 0.05), as reflected by MRTpo, MAT, Ka and tmax. However, oral bioavailability (+/- SE) declined significantly (P < 0.05) from 99.6 +/- 3.69% at 0.5 months to 14.5 +/- 1.40% at 5 months of age. To evaluate a dose effect on the pharmacokinetic parameters, a series of oral doses (5, 10, 20 and 40 mg/kg) were administered to these foals at 1 month of age. beta(po) (0.548 +/- 0.023 h-1) and F (68.26 +/- 2.43%) were not affected significantly by the size of the dose. Cmax was approximately doubled with each two-fold increase in dose: 3.15 +/- 0.15, 5.84 +/- 0.48, 12.17 +/- 0.93 and 19.71 +/- 2.19 micrograms/mL. Dose-dependent kinetics were observed in MRTpo, MAT, Ka and tmax.