How to Determine the Role of the Microbiome in Drug Disposition

• Published in: Drug metabolism and disposition Vol. 46; no. 11; pp. 1588 - 1595
• Main Authors: Bisanz, Jordan E., Spanogiannopoulos, Peter, Pieper, Lindsey M., Bustion, Annamarie E., Turnbaugh, Peter J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018; American Society for Pharmacology and Experimental Therapeutics, Inc; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Animals; Drug development; Drug Discovery - methods; Drug metabolism; Environmental factors; Environmental impact; Excretion; Gastrointestinal Microbiome - physiology; Humans; In vivo methods and tests; Inactivation, Metabolic - physiology; Medicine; Metabolism; Microbiomes; Pharmaceutical Preparations - metabolism; Pharmacology; Precision medicine; Special Section – New Models in Drug Metabolism and Transport; BBB; PXR
• ISSN: 0090-9556; 1521-009X; 1521-009X
• DOI: 10.1124/dmd.118.083402

With a paradigm shift occurring in health care toward personalized and precision medicine, understanding the numerous environmental factors that impact drug disposition is of paramount importance. The highly diverse and variant nature of the human microbiome is now recognized as a factor driving interindividual variation in therapeutic outcomes. The purpose of this review is to provide a practical guide on methodology that can be applied to study the effects of microbes on the absorption, distribution, metabolism, and excretion of drugs. We also highlight recent examples of how these methods have been successfully applied to help build the basis for researching the intersection of the microbiome and pharmacology. Although in vitro and in vivo preclinical models are highlighted, these methods are also relevant in late-phase drug development or even as a part of routine after-market surveillance. These approaches will aid in filling major knowledge gaps for both current and upcoming therapeutics with the long-term goal of achieving a new type of knowledge-based medicine that integrates data on the host and the microbiome.