Population pharmacokinetics of marbofloxacin in horses: preliminary analysis.
Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microg/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC(90) of Enterobacteriacae (0.027 microg/mL).
Peyrou
M
M
Département de biomédecine vétérinaire, Faculté de médicine vétérinaire, Université de Montréal, St-Hyacinthe, Canada.
Doucet
M Y
MY
Vrins
A
A
Concordet
D
D
Schneider
M
M
Bousquet-Mélou
A
A
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005756:Gastritis / Q000188:drug therapy / Q000662:veterinary; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism*; D006736:Horses / Q000378:metabolism*; D007273:Injections, Intramuscular; D008297:Male; D008413:Mastitis / Q000188:drug therapy / Q000662:veterinary; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012044:Regression Analysis; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000662:veterinary; D059005:Topoisomerase II Inhibitors
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; C080260:marbofloxacin