Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to dairy goats

Abstract

Twelve (12) lactating dairy goats (46-71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two-period crossover design, with a 2-week washout between injections. After another 2-week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half-lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half-life after an i.v. dose of 2.2 mg/kg in non-lactating does was 254 min. The AUC0-infinity was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half-lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC0-infinity was dose-proportional from 1.1-2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by Cmax, and serum concentrations were dose-proportional after the multiple dosing regimen.

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., ). Nevertheless, conventional pharmacokinetic studies concentrated upon the total ceftiofur and metabolites rather than unbound drugs.…”

Ceftiofur Distribution in Plasma and Tissues Following Subcutaneously Administration in Ducks

“…Due to the safety of residue in edible tissues and milk, ceftiofur was approved for use in the United States in cattle, pigs, poultry, horses, dogs, goat, and sheep [5][6][7]11]. Ceftiofur has been world-widely used for cattle to treat bovine respiratory disease associated with Pasteurella hemolytica, Pasteurella multocida, and Haemophilus somnus, for swine to treat pleuropneumonia caused by Actinobacillus pleuropneumonia, and for chickens to treat fowl typhus and diarrhea associated with Salmonella Garinarium and Escherichia coli [10,18].…”

Pharmacokinetic and pharmacodynamic characterization of ceftiofur crystalline‐free acid following subcutaneous administration in domestic goats

“…injections at 4‐day interval of CCFA at the dosage of 6.6 mg/kg have been recommended to maintain therapeutic blood concentrations for 10 days (Collard et al ., ). Comparing this study to other ceftiofur PK studies, the C max (3.29 μg⁄mL) was lower than that of calves (6.02 μg⁄mL), but was higher than that of sheep (2.4 μg⁄mL) and of earlier reported value of 2.25 μg⁄mL with CCFA dosing in goats (Courtin et al ., ; Washburn et al ., ; Dore et al ., ; Rivera‐Garcia et al ., ). These differences might have been resulted due to difference in origin and breed of goats and site of injection used in two studies.…”