ORIGINAL PAPERS: Therapeutic aspectsEffects of orally administered antibiotics on the bioavailability of amlodipine gut microbiota-mediated drug interactionYoo, Hye Hyuna,*; Kim, In Sooka,*; Yoo, Dae-Hyeongb; Kim, Dong-HyunbAuthor Information aInstitute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University bDepartment of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, South Korea *Hye Hyun Yoo and In Sook Kim contributed equally to the writing of this article. Correspondence to Professor Dong-Hyun Kim, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130–701, South Korea. Tel: +82 2 961 0374; fax: +82 2 966 3885; e-mail: firstname.lastname@example.org Abbreviations: AUC, area under the plasma concentration time curve;Cmax, maximum plasma concentration;DDIs, drug–drug interactions;HPLC, high-performance liquid chromatography;LC-MS/MS, liquid chromatography-tandem mass spectrometry;P-gp, P-glycoprotein Received 17 July, 2015 Revised 11 September, 2015 Accepted 11 September, 2015 Journal of Hypertension: January 2016 - Volume 34 - Issue 1 - p 156-162 doi: 10.1097/HJH.0000000000000773 Buy Metrics Abstract Background: Amlodipine is a representative calcium channel blocker that is frequently prescribed for the treatment of hypertension. In this study, the possibility of drug–drug interactions between amlodipine and coadministered antibiotics (ampicillin) was investigated in rats; thus, changes in the metabolic activities of gut microflora and the consequent pharmacokinetic pattern of amlodipine following ampicillin treatment were characterized. Methods and results: In human and rat fecalase incubation samples, amlodipine was metabolized to yield a major pyridine metabolite. The remaining amlodipine decreased and the formation of pyridine metabolite increased with incubation time, indicating the involvement of gut microbiota in the metabolism of amlodipine. Pharmacokinetic analyses showed that systemic exposure of amlodipine was significantly elevated in antibiotic-treated rats compared with controls. Conclusion: These results showed that antibiotic intake might increase the bioavailability of amlodipine by suppressing gut microbial metabolic activities, which could be followed by changes in therapeutic potency. Therefore, coadministration of amlodipine with antibiotics requires caution and clinical monitoring. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.