Reed M D
Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106-6010, USA.
Postgrad Med. 2000 Dec;108(7 Suppl Contemporaty):17-24. doi: 10.3810/pgm.12.2000.suppl10.52.
Successful pharmacotherapy for respiratory tract (and other) infections should integrate both the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of antimicrobial agents. Antibiotics can be classified according to their pattern of antimicrobial activity: concentration-dependent killing, time-dependent killing, or a hybrid pattern. With the concentration-dependent killing pattern, the higher the drug concentration relative to pathogen minimum inhibitory concentration (MIC), the greater the rate and extent of antimicrobial activity. The time-dependent killing pattern is dependent on the duration of pathogen exposure to an antibiotic. The hybrid pattern of antimicrobial activity involves both the duration of pathogen exposure to the antibiotic and a prolonged, persistent post-antibiotic effect. The aminoglycosides and fluoroquinolones exhibit concentration-dependent killing. Thus, the main PK-PD parameters that correlate with their efficacy are the ratio of peak serum drug concentration to MIC and the ratio of the area under the concentration versus time curve to MIC. The percentage of time during the dosing interval that serum drug concentrations exceed the MIC is the only PK-PD parameter that correlates with beta-lactam efficacy. Knowledge of these PK-PD parameters is of value in optimizing the dosing regimens for all antimicrobial agents.
呼吸道（及其他）感染的成功药物治疗应综合考虑抗菌药物的药代动力学（PK）和药效学（PD）特性。抗生素可根据其抗菌活性模式进行分类：浓度依赖性杀菌、时间依赖性杀菌或混合模式。在浓度依赖性杀菌模式下，相对于病原体最低抑菌浓度（MIC），药物浓度越高，抗菌活性的速率和程度就越大。时间依赖性杀菌模式取决于病原体接触抗生素的持续时间。抗菌活性的混合模式既涉及病原体接触抗生素的持续时间，也涉及抗生素后效应的延长和持续。氨基糖苷类和氟喹诺酮类表现出浓度依赖性杀菌。因此，与其疗效相关的主要PK-PD参数是血清药物峰浓度与MIC的比值以及浓度-时间曲线下面积与MIC的比值。给药间隔期间血清药物浓度超过MIC的时间百分比是与β-内酰胺类药物疗效相关的唯一PK-PD参数。了解这些PK-PD参数对于优化所有抗菌药物的给药方案具有重要价值。
