Pharmacokinetics of the amoxicillin-clavulanic acid combination after intravenous and oral administration in cats

J Vet Pharmacol Ther. 2019 Sep;42(5):511-517. doi: 10.1111/jvp.12765. Epub 2019 Jun 4.

Abstract

The pharmacokinetic properties of amoxicillin (AMX) and clavulanic acid (CLV) were studied in healthy cats following single intravenous and oral dosage of 10 mg/kg of AMX and 2.5 mg/kg of CLV. The drug concentrations in plasma were determined by a high-performance liquid chromatographic-tandem mass spectrometry (LC-MS-MS) method validated for canine plasma and further subjected to noncompartmental analysis. After intravenous injection, no significant difference (p > 0.05) was found in the volume of distribution of these two compounds. In addition, AMX and CLV were both rapidly eliminated from plasma with a clearance of 0.453 and 0.921 L hr-1 kg-1 , respectively; however, a quicker elimination was observed for CLV (p < 0.01). After oral administration, both drugs were characterized by rapid absorption with an absorption half-life of 1.10 and 0.70 hr for AMX and CLV, respectively. Significant differences were observed between their absorption rates (p < 0.05). However, the oral bioavailabilities of AMX and CLV (75.57% and 98.15%, respectively) were not statistically different (p > 0.05). A total intravenous or oral dose at 12.5 mg/kg of AMX and CLV (4:1) is predicted to be effective for treating those bacterial species isolated from cats with a minimum inhibitory concentration (MIC) of ≤0.25 μg/ml for 12 hr, based on a time above the MIC (T > MIC) of 40%.

Keywords: amoxicillin; cats; clavulanic acid; oral bioavailability; pharmacokinetics.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Administration, Oral
  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage
  • Amoxicillin-Potassium Clavulanate Combination / blood
  • Amoxicillin-Potassium Clavulanate Combination / pharmacokinetics*
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Cats / blood*
  • Cross-Over Studies
  • Female
  • Half-Life
  • Injections, Intravenous
  • Male

Substances

  • Anti-Bacterial Agents
  • Amoxicillin-Potassium Clavulanate Combination