Concentration of ceftiofur metabolites in the plasma and lungs of horses following intramuscular treatment

Abstract

Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved for veterinary use, is metabolized to desfuroylceftiofur which is conjugated to micro as well as macromolecules. Twelve horses, weighting 442-618 kg, were injected intramuscularly with a single dose of 2.2 mg ceftiofur/kg (1.0 mg/lb) body weight. Blood was collected at various intervals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatment. The concentration of desfuroylceftiofur and desfuroylceftiofur conjugates in the plasma and lungs was determined by converting them to desfuroylceftiofur acetamide (DCA) and measured DCA by high performance liquid chromatography with UV detection. The average maximum concentration (Cmax) of desfuroylceftiofur and related metabolites in plasma expressed as ceftiofur equivalents was 4.46 +/- 0.93 micrograms/ml occurred at 1.25 +/- 0.46 h after treatment. These concentrations declined to 0.99 +/- 0.16, 0.47 +/- 0.15 and 0.17 +/- 0.02 microgram/ml at 8, 12, and 24 h, respectively. The mean residence time of ceftiofur metabolites was 6.10 +/- 1.27 h. Concentrations of desfuroylceftiofur and desfuroylceftiofur conjugates in the lungs of horses expressed as ceftiofur equivalents were 1.40 +/- 0.36, 0.27 +/- 0.07, and 0.15 +/- 0.08 micrograms/ml at 1, 12, and 24 h, respectively. These concentrations of the drug at 12 and 24 h in lung homogenate were similar but slightly lower than plasma concentrations in the same horses, and the plasma pharmacokinetic values including half-life were similar to those observed at the approved dose of 1.1-2.2 mg ceftiofur/kg body weight administered intramuscularly once daily for 3-5 days in cattle.

Pharmacokinetic profile of Ceftiofur Hydrochloride Injection in lactating Holstein dairy cows

“…In most species, the thioester bond of ceftiofur is rapidly cleaved by circulating enzymes to produce DFC and other related metabolites (Jaglan et al., ). The overall pharmacokinetics profile of CEF in lactating Holstein dairy cows in this study is similar to cattle, goats, and horses documented in previous studies (Courtin & Wetzlich, ; Halstead et al., ; Meyer et al., ).…”

Antimicrobial Use in Horses Undergoing Colic Surgery

“…Because of presence of active metabolites, consensus data on the half‐life of ceftiofur in adult horses after IV administration are lacking. We therefore used the most detailed information available after IM dosing to derive the half‐life for ceftiofur . Horses euthanized on the table were excluded from this part of the analysis.…”

Determination of ceftiofur in bovine plasma by HPLC-DAD

“…Previous analytical methods have extracted derivatized analyte from plasma using a single solid-phase extraction step with Oasis HLB cartridges [4], double solid-phase extraction cleanup steps with C18 and SAX cartridges [2,5], and from tissue using triple solid-phase extraction clean-up steps with C18, SAX and SCX cartridges [3], followed by HPLC analysis with results reported as ceftiofur-free acid equivalents (CFAE). The simplified method presented here involves direct injection of a cleaved and derivatized sample, a protein precipitation step, and HPLC analysis using diode-array detection (DAD) with external standardization.…”