Le Normand Y, Ganiere-Monteil C, Drugeon H, Abbas S, Mazeas M, Kergueris M F
Laboratoire de Pharmacologie, UFR de médecine de Nantes, 9, quai Moncousu, 44093 Nantes cedex 01, France.
Pathol Biol (Paris). 2004 Dec;52(10):597-601. doi: 10.1016/j.patbio.2004.07.010.
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.
药代动力学/药效学指标的解读因抗生素类别而异。为了说明这一点，我们基于临床病例模拟开发了一个多学科教程程序。该软件包含三种药物：妥布霉素、万古霉素和阿奇霉素。根据用户提出的给药方案，该模型模拟抗生素血浆浓度随时间的变化曲线（妥布霉素、万古霉素和阿奇霉素）以及组织浓度（阿奇霉素）。在稳态时计算峰浓度和谷浓度。提供注释以评估治疗效果，并帮助用户改进其妥布霉素或万古霉素的处方。计算阿奇霉素在血浆和组织中的T(> MIC)（浓度高于最低抑菌浓度的时间）和AUC(24)（浓度-时间曲线下面积）。为了在理论药代动力学和临床实践之间建立联系，我们将此模型作为抗生素监测的模拟。我们强调交互性和模拟，从而进行应用推理和决策。它说明了（i）药代动力学参数、感染部位和杀菌动力学对三种不同类别抗生素使用的影响，（ii）给药途径、剂量和给药间隔对治疗反应的作用，以及（iii）不规律给药对临床疗效的影响。
