Integretion of pharmacokinetics and pharmacodynamics in antibacterial drug development and pharmacotherapy
- VernacularTitle:药物动力学和药效动力学结合在抗菌药物研发和临床治疗中的应用
- Author:
Jun SHI
- Publication Type:Journal Article
- Keywords:
pharmacokinetics;
pharmacodynamics;
antibacterial;
in vitro model;
animal models;
Monte Carlo simulation;
model based drug development
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2007;12(10):1099-1113
- CountryChina
- Language:Chinese
-
Abstract:
There is a pressing need for new antibacterial agents due to the development of drug-resistant pathogens. Unfortunately drug development is a difficult and complicated process. The traditional approach in searching for a right dose is quite empirical, both costly and time-consuming. To enhance the ability to predict the likelihood of success for lead compound selection, in vitro pharmacodynamic and in vivo animal infection models are now extensively used. The value of these pre-clinical experiments, combined with mathematical modeling, helps to identify a pharmacokinetic (PK)-pharmacodynamic (PD) exposure measure which best predicts the therapeutic efficacy, and to quantify the magnitude of this index required for in vivo efficacy. PK-PD target attainment analyses using Monte Carlo simulation to integrate interpatient variability in drug exposure (PK), drug potency (MIC), and in vivo exposure targets that are predictive of positive therapeutic outcomes are influencing antibacterial drug development for proof of concept, for dose and dosing interval selection, for determining susceptibility breakpoints, and for evaluating the clinical meaning of antibacterial resistance. In this article, the key concepts of antibacterial PK-PD and model based antibacterial drug development strategy and process are critically reviewed.
