Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep

J Vet Pharmacol Ther. 2020 Mar;43(2):108-114. doi: 10.1111/jvp.12841. Epub 2020 Feb 11.

Abstract

In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t1/2β ), total body clearance (ClT ), volume of distribution at steady state (Vdss ) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h-1 kg-1 , 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2β and AUC of moxifloxacin, they significantly reduced the ClT and Vdss . These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.

Keywords: diclofenac; flunixin meglumine; moxifloxacin; pharmacokinetics; sheep.

MeSH terms

  • Administration, Intravenous / veterinary
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Chromatography, High Pressure Liquid / veterinary
  • Clonixin / administration & dosage
  • Clonixin / analogs & derivatives*
  • Clonixin / pharmacokinetics
  • Diclofenac / administration & dosage
  • Diclofenac / pharmacokinetics*
  • Female
  • Longitudinal Studies
  • Moxifloxacin / administration & dosage
  • Moxifloxacin / pharmacokinetics*
  • Reproducibility of Results
  • Sheep / metabolism*

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Diclofenac
  • flunixin meglumine
  • Moxifloxacin
  • Clonixin