Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos)

Abstract

Six adult male alpacas received one subcutaneous administration of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. After a washout period, the same alpacas received three subcutaneous doses of 6.6 mg/kg CCFA at 5-day intervals. Blood samples collected from the jugular vein before and at multiple time points after each CCFA administration were assayed for ceftiofur- and desfuroylceftiofur-related metabolite concentrations using high-performance liquid chromatography. Pharmacokinetic disposition of CCFA was analyzed by a noncompartmental approach. Mean pharmacokinetic parameters (± SD) following single-dose administration of CCFA were Cmax (2.7 ± 0.9 μg/mL); Tmax (36 ± 0 h); area under the curve AUC0→∞ (199.2 ± 42.1 μg·h/mL); terminal phase rate constant λz (0.02 ± 0.003/h); and terminal phase rate constant half-life t1/2λz (44.7 h; harmonic). Mean terminal pharmacokinetic parameters (±SD) following three administrations of CCFA were Cmax (2.0 ± 0.4 μg/mL); Tmax (17.3 ± 16.3 h); AUC0→∞ (216.8 ± 84.5 μg·h/mL); λz (0.01 ± 0.003/h); and t1/2λz (65.9 h; harmonic). The terminal phase rate constant and the Tmax were significantly different between single and multiple administrations. Local reactions were noted in two alpacas following multiple CCFA administrations.

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

“…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). 27 The mean Tmax for CFAE for the sheep of this study (23.1 hours) following SC administration of CCFA was comparable to that for goats 22 (26.7 healthy adult female Suffolk-crossbred sheep immediately before (0 hours) and after SC administration of CCFA (6.6 mg/kg) in the cervical region. At each time, serum samples with CFAE concentrations less than the limit of quantification (0.1 µg/mL) for the HPLC assay were not included in the calculation of the mean serum CFAE concentration.…”

“…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).…”