Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus)

Abstract

Six nonlactating and six lactating adult female goats received a single subcutaneous injection of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. Blood samples were collected from the jugular vein before and at multiple time points after CCFA administration. Milk samples were collected twice daily. Concentrations of ceftiofur and desfuroylceftiofur-related metabolites were measured using high-performance liquid chromatography. Data were analyzed using compartmental and noncompartmental approaches. The pharmacokinetics of CCFA in the domestic goat was best described by a one compartment model. Mean (±SD) pharmacokinetic parameters were as follows for the nonlactating goats: area under the concentration time curve(0-∞) (159 h·μg/mL ± 19), maximum observed serum concentration (2.3 μg/mL ± 1.1), time of maximal observed serum concentration (26.7 h ± 16.5) and terminal elimination half life (36.9 h; harmonic). For the lactating goats, the pharmacokinetic parameters were as follows: area under the concentration time curve(0-∞) (156 h·μg/mL ± 14), maximum observed serum concentration (1.5 μg/mL ± 0.4), time of maximal observed serum concentration (46 h ± 15.9) and terminal elimination half life (37.3 h; harmonic). Ceftiofur and desfuroylceftiofur-related metabolites were only detectable in one milk sample at 36 h following treatment. There were no significant differences in the pharmacokinetic parameter between the nonlactating and lactating goats.

PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE-FREE ACID (EXCEDE STERILE SUSPENSION®) ADMINISTERED VIA INTRAMUSCULAR INJECTION IN WILD CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS)

“…The pharmacokinetic data obtained from this study were similar to previously documented data described in other mammalian species. The C max (lg/ml) measured in the California sea lion (3.6) was higher than equine (0.78 6 0.19) and the Asian elephant (1.36 6 0.74), lower than beef cattle (6.39 6 1.79) and dairy cattle (4.44 6 1.65), and most comparable to levels measured in alpaca (2.7 6 0.9) and domestic goats (2.3 6 1.1) 2,5,7,9,12 In cattle, a single dose of EXCEDE has been documented to provide plasma drug levels .0.2 lg/ml in order to target common respiratory Table 2. Pharmacokinetic results after a single intramuscular dose at 6.6 mg/kg of ceftiofur crystalline-free acid administered to California sea lions.…”

“…4,5,7,9 This longer terminal half-life and prolonged efficacious concentration of CCFA is due to ''flip-flop kinetics,'' wherein the rate of elimination is dependent on the slower absorption rate. 19 Because of the lack of published intravenous data for immediate-release ceftiofur formulations in the sea lion, which is needed to determine the intrinsic elimination rate of ceftiofur, it is unknown whether the observed pharmacokinetic profile after CCFA administration exhibits flip-flop kinetics.…”

“…It is also approved in Europe under the trade name Naxcelt. Investigations have also evaluated the use of the drug in other 7,9 The prolonged duration of action, because of its extended release properties, is attractive for use in wildlife species requiring less frequent injections to minimizing handling and stress. Use of EXCEDE in nondomestic species is increasing, and pharmacokinetic analysis and safety have been reported in Asian elephants (Elephas maximus), ball pythons (Python regius), helmeted guinea fowl (Numida meleagris), and American black ducks (Anas rubripes).…”

Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous administration of a single dose to sheep

“…However, the time that the serum CFAE concentration remained greater than the target MIC varied substantially among the study sheep, a phenomenon that has also been described in goats 22 and neonatal foals, 23 although the target MICs used in those studies 22,23 were species-specific and differed from that used in the present study. However, the time that the serum CFAE concentration remained greater than the target MIC varied substantially among the study sheep, a phenomenon that has also been described in goats 22 and neonatal foals, 23 although the target MICs used in those studies 22,23 were species-specific and differed from that used in the present study.…”

“…When the pharmacokinetics of CCFA determined for the sheep of the present study was compared with the pharmacokinetics of CCFA in goats, 22 cattle, 26 alpacas, 27 and horses, 28 the pharmacokinetic profile of CCFA in sheep most closely resembled that in goats and alpacas. The mean serum Cmax of CFAE achieved after SC administration of CCFA in sheep (2.45 µg/mL) was similar to that in goats 22 (2.25 µg/mL) and alpacas 27 (2.65 µg/mL), and the mean ± SD AUC 0→∞ for the sheep of the present study (206.63 ± 24.85 µg•h/mL) was similar to the AUC 0→∞ for alpacas (199.22 ± 44.13 µg•h/mL).…”