Implications for dosing regimen of enrofloxacin administered concurrently with dexamethasone in febrile buffalo calves
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The objective of the study was to determine the influence of dexamethasone (DXM) on pharmacokinetics (PK) and pharmacodynamics (PD) of enrofloxacin (ENR) for dosage optimization following concurrent administration of ENR and DXM in febrile buffalo calves. A 2 μg/kg intravenous dosage of lipopolysaccharide derived from Escherichia coli was used to induce fever in calves. After inducing fever, ENR was administered at the dose rate of 12 mg/kg, IM followed by IM injection of DXM (0.05 mg/kg) in calves. Minor alterations in PK of ENR were observed following the administration of ENR + DXM. The PK parameters were t1/2K10 = 6.34 h, Cl/F = 0.729 L/kg/h, and MRT0−∞ = 10.5 h. Antibacterial activity (MIC, MBC, ex vivo time-kill kinetics) of ENR for P. multocida was not affected by DXM. But MPC of ENR against P. multocida was lessened in presence of DXM. Using PK–PD-modeled AUC0−24h/MIC values for bactericidal effect against P. multocida, daily dosages of ENR administered in combination with DXM were 4.02 mg/kg and 16.1 mg/kg, respectively, for MIC90s of 0.125 μg/ml and 0.50 μg/ml. A dose of 5.38 mg/kg was determined for ENR for frequently occurring P. multocida infections having ≤ MIC90 of 0.125 μg/ml and PK–PD modeled dose was comparable with the recommended ENR dose of 5 mg/kg for bovines for mild infections. It is suggested that a recommended dosage of 5–12.5 mg/kg of ENR can be used effectively in combination with DXM to treat P. multocida associated infections in buffalo calves without any risk of resistance amplification.
KeywordsBuffalo calves Dexamethasone Enrofloxacin MPC Time-kill kinetics PK–PD modeling
Compliance with ethical standards
Animal experiments were conducted humanely following national and international animal care and use committee protocols. The study was approved by the Institutional Animal Ethics Committee of Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana (Reference no. VMC/2010/IAEC/1976-92 dated 17.12.2010)
Conflict of interest
The authors declare that they have no conflict of interest.
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