Drug metabolism in drug discovery and development

• 来源期刊: 药学学报（英文版）
• 关键词: Bioactivation Drug discovery and development Drug metabolism Metabolite Pharmacokinetics Pharmacodynamics Safety Toxicity
• 年，卷（期）: 2018,（5）
• 页码范围: 721-732
• 页数: 12页
• 语种: 英文

摘要

Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharrnacokinetics (PK),pharmacodynamics (PD),and safety should be carefully considered.This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates;these include,but are not limited to,collaboration with medicinal chemists on structure-activity relationships (SAR) to overcome high clearance,using deuterium replacement to further optimize a lead,prodrug approaches to circumvent formulation and delivery difficulties,and addressing issues such as species differences in metabolism,drug-drug interactions (DDI) and formation of reactive metabolites.