Insights from pharmacokinetic models of host-microbiome drug metabolism
Year: 2019
Type: article
Abstract: Increasing evidence suggests a role of the gut microbiota in patients' response to medicinal drugs. In our recent study, we combined genomics of human gut commensals and gnotobiotic animal experiments to quantify microbiota and host contributions to drug metabolism. Informed by experimental data, we built a physiology-based pharmacokinetic model of drug metabolism that includes intestinal compartments with microbiome drug-metabolizing activity. This model successfully predicted serum levels of metabolites of three different drugs, quantified microbial contribution to systemic drug metabolite exposure, and simulated the effect of different parameters on host and microbiota drug metabolism. In this addendum, we expand these simulations to assess the effect of microbiota on the systemic drug and metabolite levels under conditions of altered host physiology, microbiota drug-metabolizing activity or physico-chemical properties of drugs. This work illustrates how and under which circumstances the gut microbiome may influence drug pharmacokinetics, and discusses broader implications of expanded pharmacokinetic models.
Source: Gut Microbes
Authors: Maria Zimmermann-Kogadeeva, Michael Zimmermann, Andrew L. Goodman
Institution: Yale University
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,060
Funders: Howard Hughes Medical Institute, European Molecular Biology Organization, Crohn's and Colitis Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
Awards: Defining the contribution of interpersonal microbial variation to drug metabolism, G2701307372, Uncovering the bacterial physiology of the human gut microbiome upon dietary perturbations, G324905436, Harnessing variation in the gut microbiota for personalized medical treatment, Harnessing variation in the gut microbiota for personalized medical treatment, G5174738151, Causes and consequences of interpersonal microbial variation, Yale Clinical and Translational Science Award
OpenAlex ID: W2978101326