title: 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).
authors.affiliation: 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.).
authors.forename: Dae-Hyoung
authors.initials: DH
authors.lastname: Yoo
authors.affiliation: 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.).
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.affiliation: 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.).
authors.forename: Thi Kim
authors.initials: TK
authors.lastname: Van Le
authors.affiliation: 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.).
authors.forename: Il-Hoon
authors.initials: IH
authors.lastname: Jung
authors.affiliation: 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.) dhkim@khu.ac.kr yoohh@hanyang.ac.kr.
authors.forename: Hye Hyun
authors.initials: HH
authors.lastname: Yoo
authors.affiliation: 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.) dhkim@khu.ac.kr yoohh@hanyang.ac.kr.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001711:Biotransformation / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology*; D006801:Humans; D008148:Lovastatin / Q000378:metabolism*; D008297:Male; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D008148:Lovastatin