[抗生素病理学评价]。

Journal de pharmacologie Pub Date : 1986-01-01
C Carbon, C Manuel, Auzeri, Chau, Colin, Coquin, Drif, Lhoste, Merioua, Rey
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引用次数: 0

摘要

确定一种新抗生素的剂量方案是困难的,因为不能在患有传染病的患者中建立剂量/效果关系。最佳剂量通常是根据体外和体内微生物毒理学和动力学研究提供的综合数据推断出来的。今后还应提供更多的数据,如:体外杀灭效应动力学、抗生素后效应、感染部位的药物浓度、志愿者和患者的杀灭血清活性;当调节给药方式时,这些参数是如何被修改的也应该被研究。一旦从经典研究中粗略地评估出最佳剂量,就必须进行调整:要么通过适当的无威胁生命感染的临床试验项目减少剂量;或者在严重感染时增加剂量,通过对现有新数据的深入分析,因为临床试验的设计、分析技术的敏感性、标准化血清杀菌试验、模拟人类感染的复杂单参数动物模型、我们对药物毒性机制的了解有所改进。建立合理的剂量方案显然需要对这个问题采取长期的多学科方法。
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[Evaluation of the posology of antibiotics].

The determination of the dose regimen of a new antibiotic is difficult because a dose/effect relationship cannot be established in patients with an infectious disease. The optimal dose is usually extrapolated from combined data provided by in vitro and in vivo microbiologic toxicologic and kinetic studies. Additional data ought to be produced in the future such as: kinetics of cidal effect in vitro, of the post antibiotic effect, of drug concentrations at the sit of infections itself, of the cidal serum activity in volunteers and patients; how these parameters are modified when modulating the mode of administration of the drug ought to be studied as well. The optimal dose, once it is roughly evaluated from classical studies, has to be adjusted: either by decreasing the dose, through an appropriate program of clinical trials with non-threatening life infections; or by increasing the dose in severe infections, through an in-depth analysis of new data available because of the improvement of: the design of clinical trials, the sensitivity of analytical techniques, the standardized serum bactericidal tests, the sophisticated monoparametric animal models simulating human infections, our knowledge of drugs mechanisms of toxicity. Establishing a rational dose regimen obviously requires a long-term multidisciplinary approach of the problem.

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