[An example of simulation for a better understanding of PK/PD relationship of antibiotics].
The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.
Le Normand
Y
Y
Laboratoire de Pharmacologie, UFR de médecine de Nantes, 9, quai Moncousu, 44093 Nantes cedex 01, France. ylenorm@sante.uni-nantes.fr
Ganiere-Monteil
C
C
Drugeon
H
H
Abbas
S
S
Mazeas
M
M
Kergueris
M F
MF
D000900:Anti-Bacterial Agents / Q000145:classification / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D017963:Azithromycin / Q000097:blood; D003198:Computer Simulation; D006801:Humans; D007239:Infections / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D014031:Tobramycin / Q000097:blood; D014640:Vancomycin / Q000097:blood
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017963:Azithromycin; D014031:Tobramycin