Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves.

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t1/2λz ) 1.85 and 3.31 hr, area under the plasma concentration-time curve (AUC0-∞ ) 15.74 and 174 hr * μg/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr-1  kg-1 , respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t1/2λz 4.74 and 3.62 hr, and AUC0-∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.

Corum O ，Yildiz R ，Ider M ，Altan F ，Ok M ，Uney K ... -  《-》

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves.

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t1/2λz ) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC0-48 ) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr-1  kg-1 , respectively. The PK parameters of ENR and DNX following IM injection were t1/2λz 21.10 and 28.41 hr, AUC0-48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC0-48CPR /AUC0-48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC0-24 /minimum inhibitory concentration (MIC) and maximum concentration (Cmax )/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.

Corum O ，Altan F ，Yildiz R ，Ider M ，Ok M ，Uney K ... -  《-》

Pharmacokinetics of cefquinome in red-eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections.

The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ) following single intravenous (IV) or intramuscular (IM) injections of 2 mg/kg body weight in red-eared slider turtles. Plasma concentrations of CFQ were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half-life (t1/2λz ) 21.73 ± 4.95 hr, volume of distribution at steady-state (Vdss ) 0.37 ± 0.11 L/kg, area under the plasma concentration-time curve (AUC0-∞ ) 163 ± 32 μg hr-1  ml-1 , and total body clearance (ClT ) 12.66 ± 2.51 ml hr-1  kg-1 . The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (Cmax ) 3.94 ± 0.84 μg/ml, time to peak concentration (Tmax ) 3 hr, t1/2λz 26.90 ± 4.33 hr, and AUC0-∞ 145 ± 48 μg hr-1  ml-1 . The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half-life and a high bioavailability in red-eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy.

Uney K ，Altan F ，Cetin G ，Aboubakr M ，Dik B ，Sayın Z ，Er A ，Elmas M ... -  《-》

Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep.

The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 ± 11.54%. The area under the curve (AUC0-∞ ) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 μg/ml in sheep.

Corum O ，Corum DD ，Er A ，Uney K ... -  《-》

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves.

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high-performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono-compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were Cmax 6.93 ± 0.58 μg/ml, Tmax 0.5 hr, t½kα 0.16 ± 0.05 hr, t½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24-hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.

Venkatachalam D ，Dumka VK ，Ranjan B 《-》