Liquid Chromatographic Determination of Desfuroylceftiofur Metabolite of Ceftiofur as Residue in Cattle Plasma

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.

Section: Sample Analysismentioning

confidence: 99%

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

Dechant¹,

Rowe²,

Byrne

et al. 2012

“…Plasma samples were analyzed using high performance liquid chromatography for ceftiofur-and desfuroylceftiofur-related metabolites (Jaglan et al, 1990). Briefly, ceftiofur-and desfuroylceftiofur-like metabolites were extracted from plasma samples as desfuroylceftiofur following addition of dithioerythritol solution.…”

Section: Drug Analysismentioning

confidence: 99%

Pharmacokinetics of ceftiofur sodium and ceftiofur crystalline free acid in neonatal foals

Hall

Tell

Wetzlich

et al. 2010

Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharmacokinetic parameters for i.v. and s.c. ceftiofur sodium were: AUC(0→∝) (86.4 ± 8.5 and 91 ± 22 h·μg/mL for i.v. and s.c., respectively), terminal elimination half-life (5.82 ± 1.00 and 5.55 ± 0.81 h for i.v. and s.c., respectively), C(max(obs)) (13 ± 1.9 μg/mL s.c.), T(max(obs)) (0.75 ± 0.4 h for s.c.). Mean (± SD) noncompartmental pharmacokinetic parameters for s.c. ceftiofur crystalline free acid were: AUC(0→∝) (139.53 ± 22.63 h·μg/mL), terminal elimination half-life (39.7 ± 14.7), C(max(obs)) (2.52 ± 0.35 μg/mL) and t(max(obs)) (11.33 ± 1.63 h). No adverse effects attributed to drug administration were observed in any foal. Ceftiofur- and desfuroylceftiofur-related metabolites reached sufficient plasma concentrations to effectively treat common bacterial pathogens isolated from septicemic foals.

“…Ceftiofur, desfuroylceftiofur and desfuroylceftiofur conjugates all have microbiological activity, and are easily converted to desfuroylceftiofur for analysis (Salmon et al, 1996). Plasma samples were analysed for ceftiofur and desfuroylceftiofur related metabolites using a modification of the method published by Jaglan et al (1990). Briefly, the method uses dithioerythritol to cleave any macromolecule bound desfuroylceftiofur also dimer, glutathione and cysteine conjugates in the serum.…”

Section: High Performance Liquid Chromatography Amazon Parrots and Comentioning

confidence: 99%

“…The plasma samples were processed as described above, according to the method published by Jaglan et al (1990) with modifications to account for radioactivity detection.…”

Section: Chick/turkey Poult Samplesmentioning

confidence: 99%

Pharmacokinetics of ceftiofur sodium in exotic and domestic avian species

Tell¹,

Harrenstien²,

Wetzlich

et al. 1998

The pharmacokinetics of ceftiofur sodium were determined in domestic chicks, turkey poults, adult cockatiels (Nymphicus hollandicus), and adult orange-winged Amazon parrots (Amazona amazonica) after subcutaneous (chicks and turkey poults and intramuscular (i.m.) dosing (cockatiels and Amazon parrots). Turkey poult data were best fit to a single exponential model with disappearance half-lives (t1/2) of 8.6, 7.4 and 5.6 h after doses of 0.12, 0.24 and 0.48 mg ceftiofur free acid equivalents (CFAE)/poult, respectively. Data from chicks were best fit to a biexponential model with primary and secondary half-lives of 2.2 and 7.5, 3.7 and 6.8, and 3.8 and 5.3 h after doses of 0.04, 0.08 and 0.16 mg CFAE/chick, respectively. Cockatiel and Amazon parrot data were best fit to a biexponential model with primary and secondary half-lives of 0.28 and 2.5, and 0.93 and 7.9 h, respectively, after doses of 10 mg CFAE/kg body weight. The maximum concentration (Cmax) and area under the concentration time curve (AUC) in chicks and poults were dose-proportional. The Cmax for cockatiels was 5.2 micrograms/mL and for Amazon parrots was 11 micrograms/mL. Clearance in cockatiels and Amazon parrots were 11.3 and 3.8 mL/min/kg, respectively, and reflected the much greater AUC seen in Amazon parrots. Clearance values of ceftiofur were similar in chicks and Amazon parrots, slightly greater in turkey poults and greatest in cockatiels. These results indicate that pharmacokinetic differences must be considered when establishing dosage regimens for different avian species.