Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Nutrition Precision in Cancer Unit, Madrid Institute for Advanced Studies in Food (IMDEA Food), Madrid 28049, Spain.
J Pharm Sci. 2018 Mar;107(3):778-784. doi: 10.1016/j.xphs.2017.10.031. Epub 2017 Oct 26.
Oral ingestion is a common, easy to access, route for therapeutic drugs to be delivered. The conception of the gastrointestinal tract as a passive physiological compartment has evolved toward a dynamic perspective of the same. Thus, microbiota plays an important role in contributing with additional metabolic capacities to its host as well as to its phenotypic heterogeneity. These adaptations in turn influence the efficacy and toxicity of a broad range of drugs. Notwithstanding, xenobiotics and therapeutic drugs affecting the microbiome's activity also significantly impact metabolism affecting different organs and tissues, and thereby drugs' toxicity/efficacy effects. Other physiological interfaces (i.e., gut, lungs, and skin) also represent complex media with features about microbiota's composition. In addition, there have been described key regulatory effects of microbes on immunotherapy, because of its potential harnessing the host immune system, mental disorders by modulating neuroendocrine systems and cancer. These alterations are responsible of physiological variations in the response(s) between individuals and populations. However, the study of population-based differences in intestinal microbial-related drug metabolism has been largely inferential. This review outlines major reciprocal implications between drugs and microbes regulatory capacities in pharmacotherapy.
口服是将治疗药物递送至体内的常见且易于获取的途径。人们对胃肠道的认识已从将其视为被动的生理腔室,逐渐发展为将其视为具有动态特征的腔室。因此,微生物群在为宿主提供额外的代谢能力以及表现出表型异质性方面发挥着重要作用。这些适应性反过来又会影响广泛的药物的疗效和毒性。尽管如此,影响微生物组活性的外源化学物质和治疗药物也会显著影响代谢,从而影响不同器官和组织的药物毒性/疗效。其他生理界面(即肠道、肺部和皮肤)也是具有微生物组成特征的复杂介质。此外,人们已经描述了微生物对免疫疗法的关键调节作用,因为它有可能利用宿主免疫系统、通过调节神经内分泌系统来治疗精神障碍和癌症。这些改变是导致个体和人群之间反应差异的原因。然而,基于人群的肠道微生物相关药物代谢研究在很大程度上仍停留在推断阶段。本综述概述了药物和微生物调节能力在药物治疗学中的主要相互影响。