期刊
GUT MICROBES
卷 11, 期 3, 页码 587-596出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2019.1667724
关键词
Gut microbiota; drug metabolism; physiology-based pharmacokinetic modeling
资金
- NIH [GM118159, GM105456]
- Center for Microbiome Informatics and Therapeutics
- Burroughs Wellcome Fund
- HHMI Faculty Scholars Program
- Swiss National Science Foundation [P2EZP3_178482, P2EZP3_162256, P300PA_177915]
- European Molecular Biology Organization [ALTF 670-2016]
- Swiss National Science Foundation (SNF) [P2EZP3_178482, P2EZP3_162256, P300PA_177915] Funding Source: Swiss National Science Foundation (SNF)
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.
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