In vivo activity of cefquinome against Riemerella anatipestifer using the pericarditis model in the duck

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.

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep

Çorum

et al. 2019

“…Since the susceptibility breakpoint of CFQ was reported as 2 μg/ml (AVID, 1999), in this study, % T > MIC was calculated up to this value. The T > MIC values of 40 to 73% for the therapeutic efficacy of CFQ were recommended (Gu et al, 2015;Guo et al, 2015;Li et al, 2016;Qiu et al, 2016;Shan, Liang, Wang, Li, & Zeng, 2014;Wang et al, 2014;Xiao et al, 2015;Zhang et al, 2019). In this study, CFQ administration alone at a dose of 2 mg/kg every 24 hr maintained the mean T > MIC value of 50.50 (49-54)% for bacteria, with MIC values of ≤0.5 µg/ ml.…”

Section: Discussionmentioning

confidence: 54%

Effect of ketoprofen co‐administration on pharmacokinetics of cefquinome following repeated administration in goats

Tekeli

Türk

Çorum

et al. 2020

The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co‐administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20‐day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high‐performance liquid chromatography by ultraviolet detection. The mean terminal elimination half‐life (t1/2ʎz), area under the concentration–time curve (AUC0–24), peak concentration (Cmax), apparent volume of distribution (Vdarea/F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t1/2ʎz of cefquinome, increased AUC0–24 and Cmax, and decreased Vdarea/F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24‐hr dosing intervals at 2 mg/kg dose of cefquinome, which co‐administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats with an inflammatory condition.

“…In this study, T > MIC was calculated using the hypothetical MIC values (0.125–2 μg/mL) that were established based on MIC 90 values of 0.016–2 μg/mL reported for susceptible horse pathogens (Thomas et al ., ) and the susceptibility breakpoint of 2 μg/mL. In vitro and in vivo animal data support T > MIC values of 40–70% between CFQ doses (Shan et al ., ; Wang et al ., ; Gu et al ., ; Guo et al ., ; Qiu et al ., ). This pharmacodynamic target was provided by the administration of 1, 2, 4, and 6 mg/kg doses of CFQ at 12‐h intervals, with MIC values of ≤0.25, ≤0.5, ≤1, and ≤1, respectively, for bacteria (Table ).…”

Section: Discussionmentioning

confidence: 97%

Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses

Üney

Altan

et al. 2016

The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125-2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration-time curves (AUC) of cefquinome showed a dose-dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half-life values (2.30-2.41 h), the mean residence time (1.77-2.25 h), the systemic clearance (158-241 mL/h/kg), and the volume of distribution at steady-state (355-431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUC /AUC ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12-h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.