Comparison of plasma pharmacokinetics and bioavailability of ceftiofur sodium and ceftiofur hydrochloride in pigs after a single intramuscular injection

Ceftiofur sodium, a broad‐spectrum cephalosporin, is active against gram‐positive and gram‐negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty‐six healthy young pigs were selected for these two‐period, two‐treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14‐day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur‐related metabolites by high‐performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration ( C max ) after administration of ceftiofur sodium was 15.8 ± 3.40 μg/mL at 0.4–4 h after injection. After administration of ceftiofur hydrochloride, the C max was 11.8 ± 1.67 μg/mL at 1–4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392 ± 0.162 μg/mL for ceftiofur hydrochloride and 0.270 ± 0.118 μg/mL for ceftiofur sodium. The mean area under the curve ( AUC ), from time 0 to the limit of quantitation ( AUC 0‐LOQ ) after ceftiofur hydrochloride administration, was 216 ± 28.0 μg·h/mL, compared to 169 ± 45.4 μg·/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 μg/mL ( t >0.2 ) was 85.3 ± 10.6 h for ceftiofur sodium and 77.2 ± 10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C max after administration of ceftiofur sodium was 28.3 ± 4.45 μg/mL at 0.33–2 h after injection. After administration of ceftiofur hydrochloride, the C max was 29.7 ± 6.72 μg/mL at 0.66–2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274 ± 0.0550 μg/mL for ceftiofur hydrochloride and 0.224 ± 0.0350 μg/mL for ceftiofur sodium. The mean AUC 0‐LOQ after ceftiofur hydrochloride administration was 382 ± 89.8 μg . h/mL compared to 302 ± 54.4 μg . h/mL after ceftiofur sodium administration. The t >0.2 was 78.9 ± 9.65 h for ceftiofur sodium and 94.2 ± 8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.