期刊
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
卷 17, 期 5, 页码 611-625出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425255.2021.1908262
关键词
Respiratory; pulmonary; drug metabolism; lung metabolism; inhaled drugs; pharmacokinetics; inhalation toxicology; pro-drug; soft drug
This article provides a comprehensive overview of xenobiotic metabolizing enzymes in the lungs, their impact on inhaled medicines, and potential strategies for drug optimization. The review highlights the importance of considering lung metabolism in drug development and the various factors that can influence lung enzyme activity. New experimental technologies for studying lung metabolism are also discussed.
Introduction The lungs possess many xenobiotic metabolizing enzymes which influence the pharmacokinetics and safety of inhaled medicines. Anticipating metabolism in the lungs provides an opportunity to optimize new inhaled medicines and overcome challenges in their development. Areas covered This article summarizes current knowledge on xenobiotic metabolizing enzymes in the lungs. The impact of metabolism on inhaled medicines is considered with examples of how this impacts small molecules, biologics and macromolecular formulation excipients. Methods for measuring and predicting xenobiotic lung metabolism are critically reviewed and the potential for metabolism to influence inhalation toxicology is acknowledged. Expert opinion Drugs can be optimized by molecular modification to (i) reduce systemic exposure using a 'soft drug' approach, (ii) improve bioavailability by resisting metabolism, or (iii) use a prodrug approach to overcome pharmacokinetic limitations. Drugs that are very labile in the lungs may require a protective formulation. Some drug carriers being investigated for PK-modification rely on lung enzymes to trigger drug release or biodegrade. Lung enzyme activity varies with age, race, smoking status, diet, drug exposure and preexisting lung disease. New experimental technologies to study lung metabolism include tissue engineered models, improved analytical capability and in silico models.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据