Fimasartan, a New Angiotensin II Receptor Blocker for Hypertension

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Published: Dec 31, 2019
Keywords:
ยาฟีมาซาแทน ความดันเลือดสูง โรคหลอดเลือดแดงแข็ง การบาดเจ็บจากการขาดเลือด ฤทธิ์ปกป้องหัวใจ ฤทธิ์ต้านการอักเสบ

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Pornpun Vivithanaporn
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand
http://orcid.org/0000-0002-2639-9545
Sirada Sihirun
Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand

Abstract

Fimasartan, an angiotensin II receptor blocker (ARB), is approved for treatment of hypertension. This drug has higher potency and longer duration than losartan. The use of 60 to 120 mg of fimasartan once daily is able to control blood pressure for 24 h. The efficacy of fimasartan in reducing blood pressure is not inferior to that of candesartan but fimasartan provides greater effect than losartan and valsartan. The combination of fimasartan with hydrochlorothiazide or amlodipine increases blood pressure reduction. The most common adverse effects of fimasartan are headache and dizziness. Fimasartan is mainly excreted in bile. The hepatic uptake of fimasartan is dependent on organic anion-transporting polypeptide (OATP)1B1 transporters, thus causing drug-drug interaction when used in combination with OATP1B1 substrates such as rifampicin and atorvastatin. In addition to anti-hypertensive effect, preclinical studies in cell culture and animal models demonstrated the anti-inflammatory effect of fimasartan, which is related to cardioprotective and neuroprotective effects on ischemic injury as well as renoprotective and anti-atherosclerotic effect. The clinical studies in Korean patients found that fimasartan was beneficial for vascular function in patients with stroke and increased glucose-dependent insulin secretion in type 2 diabetic patients.


 

Article Details

Issue
Vol. 41 No. 2 (2019): Thai Journal of Pharmacology
Section
Review Articles

Upon acceptance of an article, the Pharmacological and Therapeutic Society of Thailand will have exclusive right to publish and distribute the article in all forms and media and grant rights to others. Authors have rights to use and share their own published articles.

Author Biography

Pornpun Vivithanaporn, Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand

Research Publications

  1. Acharjee S., Branton W.G., Vivithanaporn P., Maingat F., Paul A., Dickie P., Baker G.B., Power C. (2014) HIV-1 Nef expression in microglia disrupts dopaminergic and immune functions with associated mania-like behaviors. Brain Behav Immun. 40:74-84. (Q1 in Immunology and in Neurosciences, IF 2012 = 5.612)
  2. Ontawong A., Saowakon N., Vivithanaporn P., Pongchaidecha A., Lailerd N., Amornlerdpison D., Lungkaphin A. and Srimaroeng C. (2013) Antioxidant and renoprotective effects of Spirogyra neglecta (Hassall) Kützing extract in experimental type 2 diabetic rats. Biomed Research International. Article ID 820786, 15 pages. doi:10.1155/2013/820786. (Q2 in Medicine, Research and Experimental, IF 2012 = 2.880, Formerly known as Journal of Biomedicine and Biotechnology)
  3. Polyak M.J., Vivithanaporn P., Maingat F.G., Walsh J.G., Branton W., Cohen E.A., Meeker R. and Power C. (2013) Differential type 1 interferon-regulated gene expression in the brain during AIDS: interactions with viral diversity and neurovirulence. FASEB Journal. 27(7): 2829-44. (Q1 in Biochemistry and molecularbiology, in Biology, in Cell Biology, IF 2012 = 5.704)
  4. Maingat F.G., Polyak M.J., Paul A.M., Vivithanaporn P., Noorbakhsh F., Ahboucha S., Baker G.B., Pearson K. and Power C. (2013) Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulence. FASEB Journal. 27(2): 725-37. (Q1 in Biochemistry and molecularbiology, in Biology, in Cell Biology, IF 2012 = 5.704)
  5. McCombe JA., Vivithanaporn P., Gill M. and Power C. (2013) Predictors of symptomatic HIV-associated neurocognitive disorders in universal health care. HIV Medicine. 14(2): 99-107. (Q2 in Infectious Disease, IF 2012 = 3.324)
  6. Power C.*, Hui E., Vivithanaporn P., Acharjee S. and Polyak M. (2012) Delineating HIV-associated neurocognitive disorders using transgenic models: the neuropathogenic actions of Vpr. Journal of Neuroimmune Pharmacology. 312(1-2):45-51. (Q1 in Pharmacology and Pharmacy, IF 2012 = 3.802)
  7. Vivithanaporn P., Nelles K., DeBlock L., Newman S.C., Houston S., Gill M.J. and Power C.* (2012) Hepatitis C virus coinfection increases neurological disease burden and risk of death in treated NeuroAIDS. Journal of the Neurological Sciences. 312(1-2): 45-51. (Q2 in Clinical Neurology, IF 2011 = 2.243)
  8. Vivithanaporn P.*, Gill M.J., Power C. (2011) Impact of current antiretroviral therapies on neuroAIDS. Expert Review of Anti-infective Therapy. 9(4): 371-4. (Q1 in Pharmacology and Pharmacy, IF 2011 = 3.283)
  9. Na H., Acharjee S., Jones G., Vivithanaporn P., Noorbakhsh F., Barsby N., Maingat F., Ballanyi K., Pardo C., Cohen E.A. and Power C.* (2011) Interactions between human immunodeficiency virus (HIV)-1 Vpr expression and innate immunity influence neurovirulence. Retrovirology. 8: 44. (Q1 in Virology, IF 2011 = 6.470)
  10. Vivithanaporn P., Maingat F., Lin L.T., Na H., Richardson C.D., Agrawal B., Cohen E.A., Jhamandas J.H. and Power C. (2010) Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity. PLoS ONE. 5(9). pii: e12856. (Q1 in Biology, IF 2010 = 4.411)
  11. Vivithanaporn P., Heo G., Gamble J., Krentz H.B., Hoke A., Gill M.J. and Power C.* (2010) Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology. 75(13):1150-8. (Q1 in Clinical Neurology, IF 2010 = 8.017)
  12. Lee K.+, Vivithanaporn P.+, Siemieniuk R., Krentz H.B., Maingat F., Gill M.J. and Power C.* (2010) Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS. BMC Neurology. 10:44. (Q2 in Clinical Neurology, IF 2010 = 2.797)
  13. + Both authors contributed equally to this study.
  14. Maingat F., Viappiani S., Zhu Y., Vivithanaporn P., Ellestad K.K., Holden J., Silva C. and Power C.* (2010) Regulation of Lentivirus neurovirulence by lipopolysaccharide conditioning: suppression of CXCL10 in the brain by IL-10. Journal of Immunology. 184(3):1566-74. (Q1 in Immunology, IF 2010 = 5.745)
  15. Maingat F., Vivithanaporn P., Zhu Y., Taylor A., Baker G., Pearson K. and Power C.* (2009) Neurobehavioral performance in feline immunodeficiency virus infection: integrated analysis of viral burden, neuroinflammation, and neuronal injury in cortex. Journal of Neuroscience. 29(26):8429-37. (Q1 in Neuroscience, IF 2009 = 7.178)
  16. Gill M.B., Vivithanaporn P. and Swanson G.T.* (2009) Glutamate binding and conformational flexibility of ligand-binding domains are critical early determinants of efficient kainate receptor biogenesis. Journal of Biological Chemistry. 284(2ปร1):14503-12. (Q1 in Biochemistry & Molecular Biology, IF 2009 = 5.328)
  17. Vivithanaporn P., Lash L.L., Marszalec W. and Swanson G.T.* (2007) Critical roles for the M3-S2 transduction linker domain in kainate receptor assembly and postassembly trafficking. Journal of Neuroscience. 27(39): 10423-33. (Q1 in Neuroscience, IF 2007 = 7.490)
  18. Vivithanaporn P., Yan S. and Swanson G.T.* (2006) Intracellular trafficking of KA2 kainate receptors mediated by interactions with coatomer protein complex I (COPI) and 14-3-3 chaperone systems. Journal of Biological Chemistry. 281(22): 15475-84. (Q1 in Biochemistry & Molecular Biology, IF 2006 = 5.808)

References

1. Angeli F, Verdecchia P, Trapasso M, Pane M, Signorotti S, Reboldi G. PK/PD evaluation of fimasartan for the treatment of hypertension Current evidences and future perspectives. Expert Opin Drug Metab Toxicol. 2018 May;14(5):533-41.
2. Pradhan A, Gupta V, Sethi R. Fimasartan: a new armament to fight hypertension. J Family Med Prim Care. 2019 Jul;8(7):2184-8.
3. Food and Drug Administration [Internet]. Nonthaburi: FDA; [date unknown]. Registered drug searching; 2019 Oct 8 [cited 2019 Nov 1]; Available from: https://pertento.fda.moph.go.th/FDA_SEARCH_DRUG/SEARCH_DRUG/pop-up_drug_ex.aspx?Newcode=U1DR1C1012600000911C
4. Kim TW, Yoo BW, Lee JK, Kim JH, Lee KT, Chi YH, et al. Synthesis and antihypertensive activity of pyrimidin-4(3H)-one derivatives as losartan analogue for new angiotensin II receptor type 1 (AT1) antagonists. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1649-54.
5. Dickstein K, Timmermans P, Segal R. Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure. Expert Opin Investig Drugs. 1998 Nov;7(11):1897-914.
6. Kim JH, Lee JH, Paik SH, Kim JH, Chi YH. Fimasartan, a novel angiotensin II receptor antagonist. Arch Pharm Res. 2012 Jul;35(7):1123-6.
7. Chi YH, Lee H, Paik SH, Lee JH, Yoo BW, Kim JH, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of fimasartan following single and repeated oral administration in the fasted and fed states in healthy subjects. Am J Cardiovasc Drugs. 2011 Oct 1;11(5):335-46.
8. Kim CO, Lee HW, Oh ES, Seong SJ, Kim DY, Lee J, et al. Influence of hepatic dysfunction on the pharmacokinetics and safety of fimasartan. J Cardiovasc Pharmacol. 2013 Dec;62(6):524-9.
9. Kim S, Lee J, Shin D, Lim KS, Kim YS, Jang IJ, et al. Effect of renal function on the pharmacokinetics of fimasartan: a single-dose, open-label, Phase I study. Drug Des Devel Ther. 2014 Oct 6;8:1723-31.
10. Choi Y, Lee S, Jang IJ, Yu KS. Pharmacokinetic interaction between fimasartan and atorvastatin in healthy male volunteers. Drug Des Devel Ther. 2018 Jul 24; 12:2301-9.
11. Kim JW, Yi S, Kim TE, Lim KS, Yoon SH, Cho JY, et al. Increased systemic exposure of fimasartan, an angiotensin II receptor antagonist, by ketoconazole and rifampicin. J Clin Pharmacol. 2013 Jan;53(1):75-81.
12. Rhee MY, Ahn T, Chang K, Chae SC, Yang TH, Shim WJ, et al. The efficacy and safety of co-administration of fimasartan and rosuvastatin to patients with hypertension and dyslipidemia. BMC Pharmacol Toxicol. 2017 Jan 5;18(1):2.
13. Kang WY, Kim EH, Seong SJ, Gwon MR, Yang DH, Kim HJ, et al. Pharmacokinetic drug interaction study using fimasartan and rosuvastatin in healthy volunteers. Int J Clin Pharmacol Ther. 2016 Dec;54(12):992-1003.
14. Lee HY, Oh BH. Fimasartan: a new angiotensin receptor blocker. Drugs. 2016 Jul;76(10):1015-22.
15. Ghim JL, Paik SH, Hasanuzzaman M, Chi YH, Choi HK, Kim DH, et al. Absolute bioavailability and pharmacokinetics of the angiotensin II receptor antagonist fimasartan in healthy subjects. J Clin Pharmacol. 2016 May;56(5): 576-80.
16. Jeong ES, Kim YW, Kim HJ, Shin HJ, Shin JG, Kim KH, et al. Glucuronidation of fimasartan, a new angiotensin receptor antagonist, is mainly mediated by UGT1A3. Xenobiotica. 2015 Jan;45(1):10-18.
17. Choi YJ, Lee JY, Ryu CS, Chi YH, Paik SH, Kim SK. Role of cytochrome P450 enzymes in fimasartan metabolism in vitro. Food Chem Toxicol. 2018 May;115: 375-84.
18. Yamashiro W, Maeda K, Hirouchi M, Adachi Y, Hu Z, Sugiyama Y. Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos. 2006 Jul;34(7):1247-54.
19. Yamada A, Maeda K, Kamiyama E, Sugiyama D, Kondo T, Shiroyanagi Y, et al. Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
20. Ishiguro N, Maeda K, Saito A, Kishimoto W, Matsushima S, Ebner T, et al. Establishment of a set of double transfectants coexpressing organic anion transporting polypeptide 1B3 and hepatic efflux transporters for the characterization of the hepatobiliary transport of telmisartan acylglucuronide. Drug Metab Dispos. 2008 Apr;36(4):796-805.
21. Shin KH, Kim TE, Kim SE, Lee MG, Song IS, Yoon SH, et al. The effect of the newly developed angiotensin receptor II antagonist fimasartan on the pharmaco-kinetics of atorvastatin in relation to OATP1B1 in healthy male volunteers. J Cardiovasc Pharmacol. 2011 Nov;58(5):492-9.
22. Werner D, Werner U, Meybaum A, Schmidt B, Umbreen S, Grosch A, et al. Determinants of steady-state torasemide pharmacokinetics: impact of pharmaco- genetic factors, gender and angiotensin II receptor blockers. Clin Pharmacokinet. 2008 May;47(5):323-32.
23. Abraham HM, White CM, White WB. The comparative efficacy and safety of the angiotensin receptor blockers in the management of hypertension and other cardiovascular diseases. Drug Saf. 2015 Jan;38(1):33-54.
24. Huang F, Marzin K, Koenen R, Kammerer KP, Strelkowa N, Elgadi M, et al. Effect of steady-state faldaprevir on pharmacokinetics of atorvastatin or rosuvastatin in healthy volunteers: a prospective open-label, fixed-sequence crossover study. J Clin Pharmacol. 2017 Oct;57(10):1305-14.
25. Kang WY, Seong SJ, Ohk B, Gwon MR, Kim BK, Cho S, et al. Pharmacokinetic and bioequivalence study comparing a fimasartan/rosuvastatin fixed-dose combination with the concomitant administration of fimasartan and rosuvastatin in healthy subjects. Drug Des Devel Ther. 2018 Oct 26;12:3607-15.
26. Lee J, Han S, Jeon S, Hong T, Yim DS. Pharmacokinetic-pharmacodynamic model of fimasartan applied to predict the influence of a high fat diet on its blood pressure-lowering effect in healthy subjects. Eur J Clin Pharmacol. 2013 Jan; 69(1):11-20.
27. Burnier M. Angiotensin II type 1 receptor blockers. Circulation. 2001 Feb 13; 103(6):904-12.
28. Park JB, Sung KC, Kang SM, Cho EJ. Safety and efficacy of fimasartan in patients with arterial hypertension (Safe-KanArb study): an open-label observational study. Am J Cardiovasc Drugs. 2013 Feb;13(1):47-56.
29. Lee H, Kim KS, Chae SC, Jeong MH, Kim DS, Oh BH. Ambulatory blood pressure response to once-daily fimasartan: an 8-week, multicenter, randomized, double-blind, active-comparator, parallel-group study in Korean patients with mild to moderate essential hypertension. Clin Ther. 2013 Sep;35(9):1337-49.
30. Cardona-Munoz EG, Lopez-Alvarado A, Conde-Carmona I, Sanchez-Mejorada G, Pascoe-Gonzalez S, Banda-Elizondo RG, et al. Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension. Arch Cardiol Mex. 2017 Oct-Dec;87(4):316-25.
31. Park DH, Yun GY, Eun HS, Joo JS, Kim JS, Kang SH, et al. Fimasartan-induced liver injury in a patient with no adverse reactions on other types of angiotensin II receptor blockers: A case report. Medicine (Baltimore). 2017 Nov;96(47):e8905.
32. Han SE, Jeong SH, Kang HJ, Hong MS, Paek E, Cho H, et al. Safety and efficacy of fimasartan with essential hypertension patients in real world clinical practice: data from a post marketing surveillance in Korea. Transl Clin Pharmacol. 2018 Sep;26(3):118-27.
33. Kanarb [package insert]. Bangkok:Zuellig Pharma; 2017.
34. Kim TH, Kim MG, Shin S, Chi YH, Paik SH, Lee JH, et al. Placental transfer and mammary excretion of a novel angiotensin receptor blocker fimasartan in rats. BMC Pharmacol Toxicol. 2016 Jul 26;17(1):35.
35. Lee H, Yang HM, Lee HY, Kim JJ, Choi DJ, Seung KB, et al. Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean Patients with hypertension: findings from Two Phase II, randomized, double-blind, placebo-controlled studies. Clin Ther. 2012 Jun;34(6):1273-89.
36. Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ, et al. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012 Mar;34(3):552-68.
37. Youn JC, Ihm SH, Bae JH, Park SM, Jeon DW, Jung BC, et al. Efficacy and safety of 30-mg fimasartan for the treatment of patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, phase III clinical study. Clin Ther. 2014 Oct 1;36(10):1412-21.
38. Lee JH, Yang DH, Hwang JY, Hur SH, Cha TJ, Kim KS, et al. A randomized, double-blind, candesartan-controlled, parallel group comparison clinical trial to evaluate the antihypertensive efficacy and safety of fimasartan in patients with mild to moderate essential hypertension. Clin Ther. 2016 Jun;38(6):1485-97.
39. Lee HY, Kim CH, Song JK, Chae SC, Jeong MH, Kim DS, et al. 24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean patients with mild to moderate essential hypertension. Korean J Intern Med. 2017 Nov;32(6):1025-36.
40. Lee HY, Kim YJ, Ahn T, Youn HJ, Chull Chae S, Seog Seo H, et al. A randomized, multicenter, double-blind, placebo-controlled, 3  3 factorial design, phase II study to evaluate the efficacy and safety of the combination of fimasartan/ amlodipine in patients with essential hypertension. Clin Ther. 2015 Nov 1;37(11): 2581-96.
41. Kim KI, Shin MS, Ihm SH, Youn HJ, Sung KC, Chae SC, et al. A randomized, double-blind, multicenter, phase III study to evaluate the efficacy and safety of fimasartan/amlodipine combined therapy versus fimasartan monotherapy in patients With essential hypertension unresponsive to fimasartan monotherapy. Clin Ther. 2016 Oct;38(10):2159-70.
42. Rhee MY, Baek SH, Kim W, Park CG, Park SW, Oh BH, et al. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy. Drug Des Devel Ther. 2015 Jun 2;9: 2847-54.
43. Lim HJ, Lee SK, Lim DY. Influence of fimasartan (a novel AT(1) receptor blocker) on catecholamine release in the adrenal medulla of spontaneously hypertensive rats. Korean J Physiol Pharmacol. 2013 Feb;17(1):99-109.
44. Uresin Y, Erbas B, Ozek M, Ozkok E, Gurol AO. Losartan may prevent the elevation of plasma glucose, corticosterone and catecholamine levels induced by chronic stress. J Renin Angiotensin Aldosterone Syst. 2004 Jun;5(2):93-6.
45. Noh HJ, Kang YS, Lim DY. Effects of losartan on catecholamine release in the isolated rat adrenal gland. Korean J Physiol Pharmacol. 2009 Aug;13(4):327-35.
46. Lim HJ, Kim SY, Lim DY. Inhibitory effects of olmesartan on catecholamine secretion from the perfused rat adrenal medulla. Korean J Physiol Pharmacol. 2010 Aug;14(4):241-8.
47. Sim DS, Jeong MH, Song HC, Kim J, Chong A, Bom HS, et al. Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction. J Korean Med Sci. 2015 Jan;30(1):34-43.
48. Lee JY, Lee CW, Kim WJ, Ahn JM, Park DW, Kang SJ, et al. Antiathero-sclerotic effects of the novel angiotensin receptor antagonist fimasartan on plaque progression and stability in a rabbit model: a double-blind placebo-controlled trial. J Cardiovasc Pharmacol. 2013 Aug;62(2):229-36.
49. Kim JH, Lim IR, Joo HJ, Park CY, Choi SC, Jeong HS, et al. Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein E knockout mice. Mol Med. 2019 July 15;25(1):33.
50. Han J, Park SJ, Thu VT, Lee SR, Long le T, Kim HK, et al. Effects of the novel angiotensin II receptor type I antagonist, fimasartan on myocardial ischemia/ reperfusion injury. Int J Cardiol. 2013 Oct 3;168(3):2851-9.
51. Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES. A novel angiotensin type I receptor antagonist, fimasartan, prevents doxorubicin-induced cardio-toxicity in rats. J Korean Med Sci. 2015 May;30(5):559-68.
52. Lim BK, Park JJ, Park SJ, Lee YJ, Kwon JS, Kim EJ, et al. Fimasartan for remodeling after myocardial infarction. J Clin Med. 2019 Mar;8(3):366.
53. Kim CK, Yang XL, Kim YJ, Choi IY, Jeong HG, Park HK, et al. Effect of long-term treatment with fimasartan on transient focal ischemia in rat brain. Biomed Res Int. 2015;2015:295925.
54. Yang X, Sun J, Kim TJ, Kim YJ, Ko SB, Kim CK, et al. Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuro-inflammation and brain injury after intracerebral hemorrhage. Exp Neurol. 2018 Dec;310:22-32.
55. Kim S, Kim SJ, Yoon HE, Chung S, Choi BS, Park CW, et al. Fimasartan, a novel angiotensin-receptor blocker, protects against renal inflammation and fibrosis in mice with unilateral ureteral obstruction: the possible role of Nrf2. Int J Med Sci. 2015 Oct 21;12(11):891-904.
56. Cho JH, Choi SY, Ryu HM, Oh EJ, Yook JM, Ahn JS, et al. Fimasartan attenuates renal ischemia-reperfusion injury by modulating inflammation-related apoptosis. Korean J Physiol Pharmacol. 2018 Nov;22(6):661-70.
57. Yang XL, Kim CK, Kim TJ, Sun J, Rim D, Kim YJ, et al. Anti-inflammatory effects of fimasartan via Akt, ERK, and NFkappaB pathways on astrocytes stimulated by hemolysate. Inflamm Res. 2016 Feb;65(2):115-23.
58. Ryu S, Shin JS, Cho YW, Kim HK, Paik SH, Lee JH, et al. Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation. Biol Pharm Bull. 2013;36(3):467-74.
59. Lee YJ, Jang YN, Han YM, Kim HM, Jeong JM, Seo HS. Fimasartan ameliorates nonalcoholic fatty liver disease through PPARdelta regulation in hyperlipidemic and hypertensive conditions. PPAR Res. 2017;2017:8048720.
60. Kim I, Park CS, Lee HY. Angiotensin II type 1 receptor blocker, fimasartan, reduces vascular smooth muscle cell senescence by Inhibiting the CYR61 signaling pathway. Korean Circ J. 2019 Jul;49(7):615-26.
61. Woo Y, Jung YJ. Angiotensin II receptor blockers induce autophagy in prostate cancer cells. Oncol Lett. 2017 May;13(5):3579-85.
62. Oh M, Lee CW, Ahn JM, Park DW, Kang SJ, Lee SW, et al. Comparison of fimasartan and amlodipine therapy on carotid atherosclerotic plaque inflammation. Clin Cardiol. 2019 Feb;42(2):241-6.
63. Choi MH, Lee JS, Lee SE, Lee SJ, Yoon D, Park RW, et al. Central and cerebral haemodynamic changes after antihypertensive therapy in ischaemic stroke patients: a double-blind randomised trial. Sci Rep. 2018 Jan 24;8(1):1556.
64. Yang YS, Lim MH, Lee SO, Roh E, Ahn CH, Kwak SH, et al. Fimasartan increases glucose-stimulated insulin secretion in patients with type 2 diabetes and hypertension compared with amlodipine. Diabetes Obes Metab. 2018 Jul; 20(7):1670-7.