Influences of flunixin and tenoxicam on the pharmacokinetics of florfenicol in lipopolysaccharide-induced endotoxemia

Abstract

The purpose of this study was to investigate the influences of flunixin (FM) and tenoxicam (TN) on the pharmacokinetics of florfenicol (FF) after coadministration in lipopolysaccharide (LPS)-induced endotoxemic rabbits. Fifteen male rabbits were used in this study. FF (20 mg/kg), FM (2 mg/kg), and TN (1 mg/kg) were coadministered via intravenous injection to the animals. The concentrations of FF were determined by high-performance liquid chromatography with diode-array detection from 0.08 to 12 h in plasma. The plasma concentration-time profile of FF was described using a noncompartmental open model. In this study, terminal half-life, area under the curve, mean residence time, and volume of distribution at steady state were significantly increased, whereas total body clearance was decreased in coadministered groups. In conclusion, FM and TN have effects on the pharmacokinetics of FF in coadministered endotoxemic rabbits. When FF is coadministered with FM and TN, it can be given at a dose of 20 mg/kg b.w. every 8 h for treatment of infections caused by susceptible pathogens with a minimum inhibitory concentration (MIC) of ≤2 µg/mL or 12 h for treatment of infections caused by susceptible pathogens with MIC of ≤1 µg/mL in critically ill rabbits. Further studies are necessary to determine variations in dosage regimens.

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration

“…The distribution and elimination half‐lives, 0.132 ± 0.0289 hr and 2.78 ± 0.166 hr, were in agreement with results previously reported in pigs (Liu et al., ). Fast elimination was also observed in other species of animals, dog 3.09 ± 0.13 hr (Birdane & Birdane, ), chicken 0.73 ± 0.08 to 1.07 ± 0.07 hr (Poźniak et al., ), llamas 2.2 hr (Pentecost, Niehaus, Werle, & Lakritz, ), rabbit 2.69 ± 0.38 hr (Koç, Atila, Karakuş, & Üney, ), sheep 1.01 ± 0.09 hr (Lane et al., ), respectively.…”

Pharmacokinetic Behavior and Pharmacokinetic/Pharmacodynamic Integration of Danofloxacin Following Single or Co-Administration with Meloxicam in Healthy Lambs and Lambs with Respiratory Infections

“…These changes may lead to the development of resistance to antibiotics, the emergence of undesirable effects, and a suboptimal level of drug exposure, leading to failure in the treatment of infection [28,29]. Although there are many studies investigating the effects of NSAIDs on the pharmacokinetics of antibiotics in healthy animals [30][31][32][33][34][35][36], studies conducted in the case of disease are limited [37][38][39]. We hypothesized that the effect of meloxicam on the pharmacokinetics of danofloxacin will change with the systemic inflammatory response caused by respiratory infection in lambs, and that the results obtained will contribute to the rational use of danofloxacin.…”

Plasma disposition of florfenicol after intramuscular administration in rabbits pretreated with pentoxifylline

“…Thus, a combined solution containing florfenicol 300 mg/mL and flunixin 16.5 mg/mL is commercially available for treating respiratory infections in cattle and pigs (Papich, 2018). Previous reports have shown that flunixin and tenoxicam modified the pharmacokinetics of florfenicol when these drugs were coadministered with this antimicrobial drug (Koc et al, 2015). Due to the inhibitory effects on renal prostaglandin synthesis, NSAIDs can decrease renal blood flow during infection and septic shock (Huh et al, 2013).…”