Affiliation:
1. Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
Abstract
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.
Science
, this issue p.
eaat9931
Funder
Howard Hughes Medical Institute
NIH Office of the Director
National Institute of General Medical Sciences
National Institute of Allergy and Infectious Diseases
Burroughs Wellcome Fund
Pew Charitable Trusts
Yale Cancer Center
Center for Microbiome Informatics and Therapeutics
Swiss National Science Foundation
EMBO
Publisher
American Association for the Advancement of Science (AAAS)
Reference27 articles.
1. Prediction of Solubility and Permeability Class Membership: Provisional BCS Classification of the World’s Top Oral Drugs
2. Revised Estimates for the Number of Human and Bacteria Cells in the Body
3. Mechanism-based inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil in the presence of NADPH;Nishiyama T.;Mol. Pharmacol.,2000
4. Effect of (E)-5-(2-bromovinyl)uracil on the catabolism and antitumor activity of 5-fluorouracil in rats and leukemic mice;Desgranges C.;Cancer Res.,1986
5. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency
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