PMID- 32546973 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20220415 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 14 DP - 2020 TI - A Pharmacokinetic Drug Interaction Between Fimasartan and Linagliptin in Healthy Volunteers. PG - 2101-2111 LID - 10.2147/DDDT.S248205 [doi] AB - OBJECTIVE: Fimasartan, an angiotensin II type 1 receptor blocker, and linagliptin, a dipeptidyl-peptidase-4 inhibitor, are frequently coadministered to treat patients with hypertension and diabetes, respectively. This study sought to evaluate the pharmacokinetic interactions between fimasartan and linagliptin after co-administration in healthy Korean subjects. METHODS: The overall study was divided into two separate parts, with each part designed as an open-label, multiple-dose, two-period, and single-sequence study. In Part A, to investigate the effect of linagliptin on fimasartan, 25 subjects received 120 mg fimasartan alone once daily for seven days during Period I, and 120 mg fimasartan with 20 mg linagliptin for seven days during Period II. In Part B, to examine the effect of fimasartan on linagliptin, 12 subjects received only linagliptin once daily for seven days during Period I, followed by concomitant administration of fimasartan for seven days during Period II, at the same doses used in Part A. Serial blood samples were collected at scheduled intervals for up to 24 h after the last dose to determine the steady-state pharmacokinetics of both drugs. RESULTS: Thirty-six subjects completed the study. The geometric mean ratio and 90% confidence intervals for maximum plasma concentration at steady state (C(max,ss)) and area under the concentration-time curve at steady state (AUC(tau,ss)) of fimasartan with or without linagliptin were 1.2633 (0.9175-1.7396) and 1.1740 (1.0499-1.3126), respectively. The corresponding values for C(max,ss) and AUC(tau,ss) of linagliptin with or without fimasartan were 0.9804 (0.8480-1.1336) and 0.9950 (0.9322-1.0619), respectively. A total of eight adverse events (AEs) were reported and the incidence of AEs did not increase significantly with co-administration of the drugs. CONCLUSION: Our results suggest that there are no clinically significant pharmacokinetic interactions between fimasartan and linagliptin when co-administered. Treatments were well tolerated during the study, with no serious adverse effects. CLINICAL TRIAL REGISTRY: http://clinicaltrials.gov, NCT03250052. CI - (c) 2020 Kang et al. FAU - Kang, Woo Youl AU - Kang WY AUID- ORCID: 0000-0002-3190-3451 AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Lee, Hae Won AU - Lee HW AUID- ORCID: 0000-0001-7299-5332 AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Gwon, Mi-Ri AU - Gwon MR AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Cho, Seungil AU - Cho S AUID- ORCID: 0000-0003-4216-7805 AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Shim, Wang-Seob AU - Shim WS AUID- ORCID: 0000-0002-0903-1386 AD - Kyung Hee Drug Analysis Center, Kyung Hee University, Seoul, Republic of Korea. FAU - Lee, Kyung-Tae AU - Lee KT AUID- ORCID: 0000-0002-3141-3727 AD - Kyung Hee Drug Analysis Center, Kyung Hee University, Seoul, Republic of Korea. FAU - Yang, Dong Heon AU - Yang DH AD - Division of Cardiology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea. FAU - Seong, Sook Jin AU - Seong SJ AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Yoon, Young-Ran AU - Yoon YR AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. AD - Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea. LA - eng SI - ClinicalTrials.gov/NCT03250052 PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial DEP - 20200526 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Biphenyl Compounds) RN - 0 (Pyrimidines) RN - 0 (Tetrazoles) RN - 3X29ZEJ4R2 (Linagliptin) RN - P58222188P (fimasartan) SB - IM MH - Administration, Oral MH - Adult MH - Biphenyl Compounds/administration & dosage/blood/*pharmacokinetics MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Healthy Volunteers MH - Humans MH - Linagliptin/administration & dosage/blood/*pharmacokinetics MH - Male MH - Middle Aged MH - Pyrimidines/administration & dosage/blood/*pharmacokinetics MH - Tetrazoles/administration & dosage/blood/*pharmacokinetics PMC - PMC7266304 OTO - NOTNLM OT - drug-drug interaction OT - fimasartan OT - linagliptin OT - pharmacokinetics OT - safety COIS- The authors report no conflicts of interest regarding the content of this article. EDAT- 2020/06/18 06:00 MHDA- 2021/03/30 06:00 PMCR- 2020/05/26 CRDT- 2020/06/18 06:00 PHST- 2020/06/18 06:00 [entrez] PHST- 2020/06/18 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/05/26 00:00 [pmc-release] AID - 248205 [pii] AID - 10.2147/DDDT.S248205 [doi] PST - epublish SO - Drug Des Devel Ther. 2020 May 26;14:2101-2111. doi: 10.2147/DDDT.S248205. eCollection 2020.