Noordin Muhammad Akram Mohd, Najm Ahmed Abdulkareem, Dyari Herryawan Ryadi Eziwar, Law Douglas, Alwi Sharifah Sakinah Syed, Lazim Azwan Mat, Cheah Yew Hoong, Tee Thiam Tsui, Fazry Shazrul
Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia.
Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia.
Mini Rev Med Chem. 2025;25(8):579-590. doi: 10.2174/0113895575362479241231054240.
The broad-spectrum action and capacity to target drug-resistant infections make synthetic Antimicrobial Peptides (AMPs) popular therapeutic agents. Indeed, the effective use of these peptides in clinical application relies on a thorough understanding of their Pharmacokinetic (PK) and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. Despite growing research on synthetic AMPs, there is a notable gap in the literature specifically addressing their ADMET profiles. Previous reviews have not extensively covered this area, providing a vital opportunity to study synthetic AMPs' pharmacokinetics and safety, which are crucial for their therapeutic development. This review covered research studies that focused on PK and ADMET of synthetic antimicrobial peptides from several databases, including Google Scholar, SCOPUS, PubMed, and Science Direct, within the years 2020 to 2024, and 12 related research papers have been found. AMPs display a wide range of PK behaviors, including rapid renal clearance, liver-centric distribution, broad distribution with low toxicity, high kidney retention, and gradual absorption with dose-dependent toxicity. Overall, the ADMET profiles of AMPs are crucial in assessing their therapeutic potential, and continuous study is necessary to enhance their practical feasibility. An in-depth investigation of the in vivo ADMET and pharmacokinetic profiles of synthetic AMPs is presented in this review to address the current gap in the research. The findings of this study provide important insights for developing synthetic AMPs as effective antimicrobial drugs.
合成抗菌肽(AMPs)具有广谱抗菌作用以及针对耐药感染的能力,使其成为热门的治疗药物。事实上,这些肽在临床应用中的有效使用依赖于对其药代动力学(PK)和ADMET(吸收、分布、代谢、排泄和毒性)特征的全面了解。尽管对合成AMPs的研究不断增加,但文献中在专门阐述其ADMET概况方面存在显著差距。以往的综述并未广泛涵盖这一领域,这为研究合成AMPs的药代动力学和安全性提供了重要契机,而这对于它们的治疗开发至关重要。本综述涵盖了2020年至2024年期间来自多个数据库(包括谷歌学术、Scopus、PubMed和ScienceDirect)的聚焦于合成抗菌肽PK和ADMET的研究,共找到12篇相关研究论文。AMPs表现出广泛的PK行为,包括快速的肾脏清除、以肝脏为中心的分布、分布广泛且毒性低、肾脏潴留高以及吸收缓慢且具有剂量依赖性毒性。总体而言,AMPs的ADMET概况对于评估其治疗潜力至关重要,持续研究对于提高其实践可行性是必要的。本综述对合成AMPs的体内ADMET和药代动力学概况进行了深入研究,以弥补当前研究中的差距。本研究结果为将合成AMPs开发成有效的抗菌药物提供了重要见解。