Research Article

Separating host and microbiome contributions to drug pharmacokinetics and toxicity

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Science  08 Feb 2019:
Vol. 363, Issue 6427, eaat9931
DOI: 10.1126/science.aat9931

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Off-target drug metabolism

Anything humans swallow is exposed to the foraging and transforming activities of the gut microbiota. This applies to therapeutic drugs as well as food components and can be a major source of interpersonal variation in drug efficacy and toxicity. Zimmermann et al. found that individual drug responses depend on the genetics of an individual's microbiota. They explored the metabolism of nucleoside drugs (which are used as antivirals and antidepressants) in mice inoculated with a variety of mutant microbiota. They then modeled the pharmacokinetics in different body compartments and identified the host and microbe contributions. In some individuals, up to 70% of drug transformation can be ascribed to microbial metabolism.

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