Kamath Srinivas, Stringer Andrea M, Prestidge Clive A, Joyce Paul
UniSa Clinical & Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Expert Opin Drug Deliv. 2023 Jul-Dec;20(10):1315-1331. doi: 10.1080/17425247.2023.2233900. Epub 2023 Jul 7.
The trillions of microorganisms that comprise the gut microbiome form dynamic bidirectional interactions with orally administered drugs and host health. These relationships can alter all aspects of drug pharmacokinetics and pharmacodynamics (PK/PD); thus, there is a desire to control these interactions to maximize therapeutic efficacy. Attempts to modulate drug-gut microbiome interactions have spurred advancements within the field of 'pharmacomicrobiomics' and are poised to become the next frontier of oral drug delivery.
This review details the bidirectional interactions that exist between oral drugs and the gut microbiome, with clinically relevant case examples outlining a clear motive for controlling pharmacomicrobiomic interactions. Specific focus is attributed to novel and advanced strategies that have demonstrated success in mediating drug-gut microbiome interactions.
Co-administration of gut-active supplements (e.g. pro- and pre-biotics), innovative drug delivery vehicles, and strategic polypharmacy serve as the most promising and clinically viable approaches for controlling pharmacomicrobiomic interactions. Targeting the gut microbiome through these strategies presents new opportunities for improving therapeutic efficacy by precisely mediating PK/PD, while mitigating metabolic disturbances caused by drug-induced gut dysbiosis. However, successfully translating preclinical potential into clinical outcomes relies on overcoming key challenges related to interindividual variability in microbiome composition and study design parameters.
构成肠道微生物群的数万亿微生物与口服药物和宿主健康形成动态双向相互作用。这些关系可改变药物药代动力学和药效学（PK/PD）的各个方面；因此，人们希望控制这些相互作用以最大化治疗效果。调节药物与肠道微生物群相互作用的尝试推动了“药物微生物组学”领域的进展，并有望成为口服药物递送的下一个前沿领域。
本综述详细介绍了口服药物与肠道微生物群之间存在的双向相互作用，并通过临床相关案例说明了控制药物微生物组学相互作用的明确动机。特别关注已证明在介导药物与肠道微生物群相互作用方面取得成功的新颖和先进策略。
联合使用肠道活性补充剂（如益生元和益生菌）、创新的药物递送载体以及策略性联合用药是控制药物微生物组学相互作用最有前景且临床可行的方法。通过这些策略靶向肠道微生物群，为通过精确介导PK/PD提高治疗效果提供了新机会，同时减轻药物引起的肠道生态失调导致的代谢紊乱。然而，将临床前潜力成功转化为临床结果依赖于克服与微生物组组成个体间差异和研究设计参数相关的关键挑战。
