[Bactericidal effect of colistin on Escherichia coli. Model and simulation or the pharmacokinetic-pharmacodynamic relation for prediction of efficacy in veterinary antibiotic therapy].
Pharmacodynamics studies consider three main parameters: the size of the bacterial population, the concentration of the antibiotic and the duration of its action. The pharmacodynamic characteristics of colistin were studied in vitro with Escherichia coli. The bacterial kinetics were fitted using differential equations. The mathematical model gave qualitative and quantitative information about the characteristics of the antibiotic-bacteria association. Above all, when linked to a pharmacokinetic model, the model permitted the prediction of the drug's efficiency. Simulations of various dosage levels in which the administration route, dose size, or interval between doses varied, permitted a more rational optimization than a prediction of efficacy based on the time taken to achieve antibiotic plasmatic concentrations above the minimal inhibitory concentration. Pharmacokinetic/pharmacodynamic modeling seems to be an interesting possibility for determining antibiotic dosing levels during the preclinical phase.
Renard
L
L
Unité de pharmacocinétique, laboratoire des médicaments vétérinaires, Centre national d'études vétérinaires et alimentaires, La-Haute-Marche-Javené, Fougères, France.
Gicquel
M
M
Laurentie
M
M
Sanders
P
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D003091:Colistin / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000662:veterinary*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D013997:Time Factors
D000900:Anti-Bacterial Agents; D003091:Colistin