Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates

J Vet Pharmacol Ther. 2010 Aug;33(4):383-8. doi: 10.1111/j.1365-2885.2009.01151.x.

Abstract

The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6-10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean +/- SD time to peak serum telithromycin activity (T(max)) was 1.75 +/- 0.76 h, maximum serum activity (C(max)) was 1.43 +/- 0.37 microg/mL, and terminal half-life (t(1/2)) was 3.81 +/- 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 +/- 14.5 microg/mL) than in PELF (5.07 +/- 2.64 microg/mL), and plasma (0.84 +/- 0.25 microg/mL). The MIC(90) of telithromycin for macrolide-resistant R. equi isolates (8 microg/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 microg/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC(50)=4.0 microg/mL) was significantly lower than that of clarithromycin (MIC(50)=24.0 microg/mL), azithromycin (MIC(50)=256 microg/mL) and erythromycin (MIC(50)=24 microg/mL).

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Azithromycin / pharmacokinetics
  • Bronchoalveolar Lavage / veterinary
  • Bronchoalveolar Lavage Fluid / cytology
  • Clarithromycin / pharmacokinetics
  • Drug Resistance, Bacterial
  • Epithelium / metabolism
  • Erythromycin / pharmacokinetics
  • Female
  • Horses
  • Ketolides / blood
  • Ketolides / pharmacokinetics*
  • Ketolides / pharmacology
  • Linear Models
  • Lung / metabolism*
  • Macrolides / pharmacology*
  • Male
  • Microbial Sensitivity Tests / veterinary
  • Rhodococcus equi / drug effects*

Substances

  • Anti-Bacterial Agents
  • Ketolides
  • Macrolides
  • Erythromycin
  • Azithromycin
  • Clarithromycin
  • telithromycin