Hoo Grace Si Ru, Liew Yi Xin, Kwa Andrea Lay-Hoon
Department of Pharmacy, Tan Tock Seng Hospital, Singapore.
Department of Pharmacy, Singapore General Hospital, Singapore.
Indian J Med Microbiol. 2017 Jul-Sep;35(3):340-346. doi: 10.4103/ijmm.IJMM_17_278.
While suboptimal dosing of antimicrobials has been attributed to poorer clinical outcomes, clinical cure and mortality advantages have been demonstrated when target pharmacokinetic (PK) and pharmacodynamic (PD) indices for various classes of antimicrobials were achieved to maximise antibiotic activity. Dosing optimisation requires a good knowledge of PK/PD principles. This review serves to provide a foundation in PK/PD principles for the commonly prescribed antibiotics (β-lactams, vancomycin, fluoroquinolones and aminoglycosides), as well as dosing considerations in special populations (critically ill and obese patients). PK principles determine whether an appropriate dose of antimicrobial reaches the intended pathogen(s). It involves the fundamental processes of absorption, distribution, metabolism and elimination, and is affected by the antimicrobial's physicochemical properties. Antimicrobial pharmacodynamics define the relationship between the drug concentration and its observed effect on the pathogen. The major indicator of the effect of the antibiotics is the minimum inhibitory concentration. The quantitative relationship between a PK and microbiological parameter is known as a PK/PD index, which describes the relationship between dose administered and the rate and extent of bacterial killing. Improvements in clinical outcomes have been observed when antimicrobial agents are dosed optimally to achieve their respective PK/PD targets. With the rising rates of antimicrobial resistance and a limited drug development pipeline, PK/PD concepts can foster more rational and individualised dosing regimens, improving outcomes while simultaneously limiting the toxicity of antimicrobials.
虽然抗菌药物剂量不足被认为会导致较差的临床结果，但当各类抗菌药物的目标药代动力学（PK）和药效学（PD）指标得以实现以最大化抗生素活性时，已证明在临床治愈和死亡率方面具有优势。剂量优化需要对PK/PD原则有充分的了解。本综述旨在为常用抗生素（β-内酰胺类、万古霉素、氟喹诺酮类和氨基糖苷类）的PK/PD原则提供基础，以及特殊人群（重症患者和肥胖患者）的给药考虑因素。PK原则决定了适当剂量的抗菌药物是否能到达预期的病原体。它涉及吸收、分布、代谢和消除的基本过程，并受抗菌药物理化性质的影响。抗菌药物药效学定义了药物浓度与其对病原体所观察到的效应之间的关系。抗生素效应的主要指标是最低抑菌浓度。PK与微生物学参数之间的定量关系称为PK/PD指数，它描述了给药剂量与细菌杀灭速率和程度之间的关系。当抗菌药物以最佳剂量给药以实现其各自的PK/PD目标时，已观察到临床结果有所改善。随着抗菌药物耐药率的上升和药物研发渠道的有限，PK/PD概念可以促进更合理和个体化的给药方案，改善治疗结果，同时限制抗菌药物的毒性。
