ArticleBiopharmaceutics & drug disposition2020
Effects of gut microbiota on in vivo metabolism and tissue accumulation of cytochrome P450 3A metabolized drug: Midazolam.
Article in Biopharmaceutics & drug disposition, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Microbes and medicines: interrelationships between pharmaceuticals and the gut microbiome.Gut microbes · 2026Review
- Role of the Gut Microbiome in Natural and Synthetic Drug Efficacy and Safety: A Narrative Review.Applied microbiology (Basel, Switzerland) · 2026Article
- Pharmacomicrobiomics: From Host-Microbiome-Drug Interactions to Clinical Translation in Precision Medicine.Metabolites · 2026Review
- DSS Colitis Model: Traps, Tricks, and Reporting Recommendations.Biomedicines · 2026Review
- Dietary Modulation of CYP3A4 and Its Impact on Statins and Antidiabetic Drugs: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Phenoconversion andHepatology forum · 2025Review
- Dual effects of indoxyl sulfate on modulation of human hepatic CYP3A activity, with individual differences.PloS one · 2025Article
- Integrating the gut microbiome and pharmacology.Science translational medicine · 2024Review
- Article
- The disposition of polychlorinated biphenyls (PCBs) differs between germ-free and conventional mice.Environmental toxicology and pharmacology · 2022Article
- Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial.Clinical and translational science · 2022Article
- Normal variation of the gut microbiota affects hepatic cytochrome P450 activity in mice.Pharmacology research & perspectives · 2021Article
- Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability.Clinical pharmacokinetics · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The link between drug-metabolizing enzymes and gut microbiota is well established. In particular, hepatic cytochrome P450 (CYP) 3A activities are presumed to be affected by gut microbiota. However, there is no direct evidence that the gut microbiota affects CYP3A metabolism or the clearance of clinically relevant drugs in vivo. Our purpose was to evaluate the effects of gut microbiota on in vitro and in vivo drug metabolism and on the clearance of midazolam, which is a standard CYP3A metabolized drug. Hepatic Cyp3a activity and in vitro midazolam hydroxylase activity were compared using specific pathogen-free (SPF) and germ-free (GF) mice. In a pharmacokinetics (PK) study, SPF and GF mice were intraperitoneally injected with 60 mg/kg of midazolam, and plasma and tissue concentrations were measured. Hepatic Cyp3a activity and midazolam hydroxylase activity were significantly lower in GF mice than in SPF mice. Notably, in the PK study, the area under the plasma concentration-time curve from time zero to infinity and the elimination half-life were approximately four-fold higher in GF mice compared with SPF mice. Furthermore, the concentration of midazolam in the brain 180 min after administration was about 14-fold higher in GF mice compared with SPF mice. Together, our results demonstrated that the gut microbiota altered the metabolic ability of Cyp3a and the tissue accumulation of midazolam.
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