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Research ArticleArticle

Gut Microbiota-Mediated Drug Interactions between Lovastatin and Antibiotics

Dae-Hyoung Yoo, In Sook Kim, Thi Kim Van Le, Il-Hoon Jung, Hye Hyun Yoo and Dong-Hyun Kim
Drug Metabolism and Disposition September 2014, 42 (9) 1508-1513; DOI: https://doi.org/10.1124/dmd.114.058354
Dae-Hyoung Yoo
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea (D.H.Y., T.K.V.L., I.H.J., D.H.K.); and Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Korea (I.S.K., H.H.Y.)
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In Sook Kim
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea (D.H.Y., T.K.V.L., I.H.J., D.H.K.); and Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Korea (I.S.K., H.H.Y.)
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Thi Kim Van Le
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea (D.H.Y., T.K.V.L., I.H.J., D.H.K.); and Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Korea (I.S.K., H.H.Y.)
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Il-Hoon Jung
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea (D.H.Y., T.K.V.L., I.H.J., D.H.K.); and Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Korea (I.S.K., H.H.Y.)
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Hye Hyun Yoo
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea (D.H.Y., T.K.V.L., I.H.J., D.H.K.); and Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Korea (I.S.K., H.H.Y.)
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Dong-Hyun Kim
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea (D.H.Y., T.K.V.L., I.H.J., D.H.K.); and Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Korea (I.S.K., H.H.Y.)
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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).

Footnotes

    • Received March 31, 2014.
    • Accepted June 17, 2014.
  • D.H.Y. and I.S.K. contributed equally to this work.

  • This research was supported by a grant from Ministry of Food and Drug Safety in 2013 [12182MFDS652].

  • dx.doi.org/10.1124/dmd.114.058354.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 42 (9)
Drug Metabolism and Disposition
Vol. 42, Issue 9
1 Sep 2014
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Research ArticleArticle

Gut Microbiota-Mediated Drug Interactions with Lovastatin

Dae-Hyoung Yoo, In Sook Kim, Thi Kim Van Le, Il-Hoon Jung, Hye Hyun Yoo and Dong-Hyun Kim
Drug Metabolism and Disposition September 1, 2014, 42 (9) 1508-1513; DOI: https://doi.org/10.1124/dmd.114.058354

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Research ArticleArticle

Gut Microbiota-Mediated Drug Interactions with Lovastatin

Dae-Hyoung Yoo, In Sook Kim, Thi Kim Van Le, Il-Hoon Jung, Hye Hyun Yoo and Dong-Hyun Kim
Drug Metabolism and Disposition September 1, 2014, 42 (9) 1508-1513; DOI: https://doi.org/10.1124/dmd.114.058354
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