Schentag J J, Gilliland K K, Paladino J A
State University of New York at Buffalo Clinical Pharmacokinetics Laboratory, Hochstetter 543, Amherst Campus, Buffalo, NY 14260, USA.
Clin Infect Dis. 2001 Mar 15;32 Suppl 1:S39-46. doi: 10.1086/319375.
Pharmacokinetic characteristics and pharmacodynamic properties dictate antimicrobial response and, along with natural immune responses, clinical outcomes. As new agents are developed with long half-lives, we will lose the ability to differentiate between concentration-dependent and time-dependent properties. The area under the inhibitory concentration curve (AUIC) defines drug regimens as a ratio of drug exposure to minimum inhibitory concentration (MIC) and allows them to be compared with each other. With AUIC and agents with long half-lives, these comparisons are possible regardless of chemical classification or concentration or time-dependent activity. Historical examples of reduced drug exposure from decreased doses (i.e., cefaclor, clarithromycin, and ciprofloxacin), and thus low AUIC values, directly correlate with drug resistance. In the face of rising MICs (as is occurring worldwide with Streptococcus pneumoniae), close attention to appropriate dosing and concentration above the MIC may delay and potentially even prevent antibiotic resistance. Creating selective pressure on reliable antibiotics by inappropriately reducing their doses will undoubtedly challenge these agents and may destroy entire drug classes with similar mechanisms of action or resistance.
药代动力学特征和药效学特性决定抗菌反应，并与天然免疫反应一起决定临床结果。随着半衰期长的新药物的开发，我们将失去区分浓度依赖性和时间依赖性特性的能力。抑制浓度曲线下面积（AUIC）将药物治疗方案定义为药物暴露量与最低抑菌浓度（MIC）的比值，并允许对它们进行相互比较。对于AUIC和半衰期长的药物，无论化学分类或浓度或时间依赖性活性如何，这些比较都是可能的。因剂量降低（即头孢克洛、克拉霉素和环丙沙星）导致药物暴露减少，从而AUIC值较低的历史实例与耐药性直接相关。面对不断上升的MIC（全球肺炎链球菌的情况就是如此），密切关注适当的给药以及高于MIC的浓度可能会延迟甚至预防抗生素耐药性。通过不恰当地降低可靠抗生素的剂量对其产生选择性压力无疑会挑战这些药物，并可能摧毁具有相似作用机制或耐药性的整个药物类别。
