Pharmacokinetics Of Ceftiofur Sodium Research Articles

Pharmacokinetics of ceftiofur sodium after intravenous and subcutaneous administration in pre-weaned calves

The current work was outlined to decide kinetic profile and bioavailability of ceftiofur sodium at measurements of 2.2 mg/kg. b.wt. after a single intravenous and subcutaneous injection in pre-weaned calves. Five clinically typical pre-weaned calves were utilized in this work. Serum ceftiofur concentrations were decided by utilizing high performance liquid chromatography (HPLC) strategy. The serum concentration-time curve has shown a two compartment open model. Taking after a single intravenous injection, distribution half-life (t0.5α) was 0.11 ± 0.01h, volume of distribution (Vdss) was 0.16 ± 0.004 L/kg, elimination half-life (t0.5β) was 11.07 ± 0.12h and total body clearance (CLtot) was 0.013 ± 0.005 L/kg/h. Taking after a single subcutaneous organization, ceftiofur had a peak serum concentration (Cmax) 6.64 ± 0.08 μg/ml at a time (tmax) of 3.38 ± 0.069 h, disposal half-life (t0.5el) was 2.11 ± 0.25h demonstrating the propensity of calves to eliminate ceftiofur in slow rate. Bioavailability was 77.04 ± 1.64% after subcutaneous injection indicating a good absorption of ceftiofur. Ceftiofur serum concentrations along 36 h following subcutaneous injection in the current work were exceeding the MICs of different susceptible microorganisms responsible for serious disease problems. These results demonstrating successful use of ceftiofur in pre-weaned calves.

Corrigendum to "Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection".

Corrigendum to "Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection".

Pharmacokinetics of Ceftiofur Sodium in Black-bone Silky Fowl after One Single Intravenous and Intramuscular Injection

Background: Ceftiofur is a third-generation cephalosporin antibiotic developed exclusively for veterinary applications. Although not approved in China, ceftiofur is being used extensively in an extra-label manner to treat poultry infections. Black-bone silky fowl is a unique chicken breed which is different from the common chicken breeds in both morphology and other physiology. These differences may result in varied pharmacokinetic profiles. Therefore, the present study aimed to investigate the pharmacokinetics of ceftiofur (measured by ceftiofur and its active metabolites concentrations) in black-bone silky fowl following a single intravenous or intramuscular injection of ceftiofur sodium.Methods: Ceftiofur sodium was intravenously and intramuscularly given to six healthy black-bone silky fowl at the dose of 10 mg/kg body weight. A derivatization method was used to quantify the concentrations of ceftiofur and its active metabolites (expressed as desfuroylceftiofur acetamide) in plasma samples. A non-compartmental method was used to calculate the pharmacokinetics parameters. Results: The terminal half-life (t1/2lz) was calculated as 3.19±0.28 and 3.36±0.17 h following intravenous and intramuscular injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady state (VSS) were determined as 73.79±5.83 ml/h/kg and 318.65±30.06 ml/kg, respectively. After intramuscular injection, the peak concentration (Cmax; 22.55±0.89 ìg/ml) was observed at 1.67±0.26 h and the absorption half-life (t1/2ka) and absolute bioavailability (F) were calculated as 0.40±0.13 h and 93.03%±7.07%, respectively. The current results demonstrated the rapid and complete absorption, however, poor distribution and rapid elimination of ceftiofur and its active metabolites in black-bone silky fowl.

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection.

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4kg. Each dog received either intravenous or subcutaneous injection, both at 5mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t1/2 λz ) was calculated as 7.40±0.79 and 7.91±1.53hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 39.91±4.04mlhr-1 kg-1 and 345.71±28.66ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 10.50±0.22μg/ml) was observed at 3.2±1.1hr, and the absorption half-life (t1/2 ka ) and absolute bioavailability (F) were calculated as 0.74±0.23hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T>MIC) values calculated here, an intravenous or subcutaneous dose at 5mg/kg of ceftiofur sodium once every 12hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0μg/ml.

PK/PD modeling of Ceftiofur Sodium against Haemophilus parasuis infection in pigs

BackgroundCeftiofur Sodium is widely used in China. Our aim was to determine Ceftiofur Sodium activity and optimize dosing regimens against the pathogen Haemophilus parasuis using an in vitro and ex vivo pharmacokinetics/pharmacodynamics modeling approach. By adopting these strategies, we wanted to extend the effective life of Ceftiofur Sodium in reduce drug-resistance in pigs.ResultsWe established an H. parasuis infection model in pigs, and assessed the pharmacokinetics of Ceftiofur Sodium in both healthy and infected animals. After Ceftiofur Sodium (10 mg/kg, i.m.) administration to healthy and H. parasuis-infected pigs, plasma based desfuroylceftiofur (a metabolite of Ceftiofur Sodium) was measured by High Performance Liquid Chromatography. The pharmacokinetics of Ceftiofur Sodium (desfuroylceftiofur) was consistent with a two-compartment open model, with first-order absorption. We observed no significant differences (P > 0.05) in pharmacokinetic parameters between healthy and infected pigs. Pharmacodynamics data showed that Ceftiofur Sodium was highly inhibitory against H. parasuis, with MIC, MBC, and MPC values of 0.003125, 0.0125 and 0.032 μg/mL, respectively. Desfuroylceftiofur in plasma also had strong bactericidal activity. Almost all H. parasuis cultured in plasma medium of Ceftiofur Sodium-inoculated healthy pigs, at each time point, were killed within 24 h. A weaker antibacterial activity was measured in infected-pig plasma medium at 18, 24, 36, and 48 h, after Ceftiofur Sodium inoculation. Pharmacokinetic parameters were combined with ex vivo pharmacodynamic parameters, and the bacteriostatic effect (36.006 h), bactericidal effect (71.637 h) and clearance (90.619 h) within 24 h, were determined using the Hill equation. Dose-calculation equations revealed the optimal dose of Ceftiofur Sodium to be 0.599–1.507 mg/kg.ConclusionsThere were no significant differences in Ceftiofur Sodium pharmacokinetic parameters between healthy and infected pigs, although pharmacokinetics/pharmacodynamics fitting curves showed obviously differences. The optimal dose of Ceftiofur Sodium was lower than recommended (3 mg/kg), which may provide improved treatments for Glässers disease, with lower drug-resistance possibility.

Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2mg/kg (n=6) or 4.4mg/kg (n=5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24hr after administration. Eight pony mares were re-enrolled in the study at least 3days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97±0.50μg/ml (low dose) and 7.45±1.05μg/ml (high dose). Terminal half-life was significantly (p=.014) shorter after administration of the low dose (2.91±0.59hr) than after administration of the high dose (4.10±0.72hr). The mean serum concentration of DCA from mares at time of foaling was 7.96±1.39μg/ml. The mean DCA concentration in colostrum was 1.39±0.70μg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1μg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Pharmacokinetics of ceftiofur sodium in equine pregnancy

Pharmacokinetics of ceftiofur sodium in equine pregnancy

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

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.

Pharmacokinetics of ceftiofur sodium after intramuscular or subcutaneous administration in green iguanas (Iguana iguana).

To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas. 6 male and 4 female adult green iguanas. In a crossover design, 5 iguanas received a single dose of ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours after administration. After a 10-week washout period, each iguana was given the same dose via the reciprocal administration route, and blood was collected in the same fashion. Ceftiofur free-acid equivalents were measured via high-performance liquid chromatography. The first phase intercepts were significantly different between the 2 administration routes. Mean maximum plasma concentration was significantly higher with the IM (28.6 +/- 8.0 microg/mL) than the SC (18.6 +/- 8.3 microg/mL) administration route. There were no significant differences between terminal half-lives (harmonic mean via IM route, 15.7 +/- 4.7 hours; harmonic mean via SC route, 19.7 +/- 6.7 hours) and mean areas under the curve measured to the last time point (IM route, 11,722 +/- 7,907 microg x h/mL; SC route, 12,143 +/- 9,633 microg x h/mL). Ceftiofur free-acid equivalent concentrations were maintained > or = 2 microg/mL for > 24 hours via both routes. A suggested dosing schedule for ceftiofur sodium in green iguanas for microbes susceptible at > 2 microg/mL would be 5 mg/kg, IM or SC, every 24 hours.

Pharmacokinetics of ceftiofur sodium in neonatal foals after intramuscular injection.

Pharmacokinetics of ceftiofur sodium in neonatal foals after intramuscular injection.