Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses

J Vet Pharmacol Ther. 2019 Sep;42(5):525-529. doi: 10.1111/jvp.12770. Epub 2019 Jun 20.

Abstract

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half-life, volume of distribution at steady-state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr-1 kg-1 , respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half-life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3-compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 μg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.

Keywords: antibacterial; horse; meropenem; pharmacokinetic; synovial fluid.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Half-Life
  • Horses / blood*
  • Meropenem / administration & dosage
  • Meropenem / blood
  • Meropenem / chemistry
  • Meropenem / pharmacokinetics*
  • Synovial Fluid / chemistry*

Substances

  • Anti-Bacterial Agents
  • Meropenem