Gut microbiota-mediated drug interactions between lovastatin and antibiotics
Abstract
Orally administered drugs may be metabolized by intestinal microbial enzymes before absorption into the blood. Accordingly, coadministration of drugs affecting the metabolic activities of gut microbes (e.g., antibiotics) may lead to drug-drug interactions (DDI). In this study, gut microbiota-mediated DDI were investigated by studying the pharmacokinetics of lovastatin in antibiotic-treated rats. Incubation of lovastatin with human and rat fecalase preparations produced four metabolites, M1 (demethylbutyryl metabolite), M4 (hydroxylated metabolite), M8 (the active hydroxy acid metabolite), and M9 (hydroxylated M8), indicating involvement of the gut microbiota in lovastatin metabolism. The plasma concentration-time profiles of M8 were compared after oral administration of lovastatin to control rats or those treated with either ampicillin (100 mg/kg) or an antibiotic mixture consisting of cefadroxil (150 mg/kg), oxytetracycline (300 mg/kg), and erythromycin (300 mg/kg). Pharmacokinetic analyses indicated that systemic exposure to M8 was significantly lower in antibiotic-treated rats compared with controls. In addition, fecal M8 formation decreased by 58.3 and 59.9% in the ampicillin- and antibiotic mixture-treated rats, respectively. These results suggested that antibiotic intake may reduce the biotransformation of orally administered drugs by gut microbiota and that the subsequent impact on microbiota metabolism could result in altered systemic concentrations of either the intact drug and/or its metabolite(s).
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Hydroxylation of lovastatin occurs in an animal model following coadministration of an antibiotic that depleted the microbiota.
“hydroxylation of lovastatin, albeit less well-characterized in terms of specific enzyme involvement, in an animal model following coadministration of an antibiotic that resulted in a more extreme depletion of the microbiota”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Yoo et al., 2014
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- Authors
- Yoo, D.-H., Kim, I. S., Van Le, T. K., Jung, I.-H., Yoo, H. H., & Kim, D.-H.
- Affiliations
- Kyung Hee University (KR)
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 42
- Issue
- 9
- Pages
- 1508-1513
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W2163951374
- Cited by
- 158
- References
- 27
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 15 · 2023: 16 · 2022: 14 · 2021: 15 · 2020: 22 · 2019: 17 · 2018: 13 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 1
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- PubMed (publishedVersion)
- The Royal Society of Chemistry’s Journals, Books and Databases (The Royal Society of Chemistry) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- lovastatin, drug-drug interactions, gut microbiota, drug metabolism, ampicillin, cefadroxil, oxytetracycline, erythromycin, pharmacokinetics, oral drug absorption
- MeSH terms
- Administration, Oral, Adult, Animals, Anti-Bacterial Agents, Biotransformation, Drug Interactions, Feces, Female, Humans, Lovastatin, Male, Middle Aged, Rats, Sprague-Dawley, Gastrointestinal Tract, Rats, Young Adult, Microbiota
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