Details of the Drug Combination

General Information of Drug Combination (ID: DCWVKJV)

Drug Combination Name
Irbesartan Amlodipine
Indication
Disease Entry Status REF
Hypertension Phase 1 [1]
Component Drugs Irbesartan   DMTP1DC Amlodipine   DMBDAZV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Irbesartan
Disease Entry ICD 11 Status REF
Diabetic kidney disease GB61.Z Approved [2]
Hypertension BA00-BA04 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]
High blood pressure BA00 Investigative [2]
Irbesartan Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin II receptor type-1 (AGTR1) TT8DBY3 AGTR1_HUMAN Antagonist [7]
HUMAN type-1 angiotensin II receptor (AGTR1) TTPKMXQ AGTR1_HUMAN Antagonist [8]
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Irbesartan Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [9]
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Irbesartan Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [11]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [12]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [13]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Metabolism [13]
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Irbesartan Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [11]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [14]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Expression [15]
Carbonic anhydrase 1 (CA1) OTNFBVVQ CAH1_HUMAN Decreases Activity [16]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [17]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases Expression [18]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [19]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Expression [19]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET) OTLU040A RET_HUMAN Increases Expression [20]
Type-1 angiotensin II receptor (AGTR1) OT2NRMJP AGTR1_HUMAN Affects Response To Substance [21]
Endoplasmic reticulum aminopeptidase 1 (ERAP1) OT72S99B ERAP1_HUMAN Affects Response To Substance [22]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Response To Substance [23]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Affects Response To Substance [24]
Cytochrome P450 11B2, mitochondrial (CYP11B2) OTIOLWYN C11B2_HUMAN Increases Response To Substance [25]
B2 bradykinin receptor (BDKRB2) OTOA9D3W BKRB2_HUMAN Affects Response To Substance [26]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Affects Response To Substance [27]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Affects Response To Substance [28]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Affects Response To Substance [29]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Amlodipine
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [5]
Chronic heart failure BD1Z Approved [5]
Hypertension BA00-BA04 Approved [6]
Malignant essential hypertension BA00 Approved [5]
Stroke 8B20 Investigative [5]
Amlodipine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1) TTFK1JQ CA2D1_HUMAN Blocker [30]
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Amlodipine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [31]
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Amlodipine Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [32]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Decreases Activity [32]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [33]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Decreases Activity [34]
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Increases Expression [35]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Response To Substance [36]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [37]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [38]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Affects Expression [39]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [40]
P-selectin (SELP) OTWR90PK LYAM3_HUMAN Decreases Expression [38]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Activity [40]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Activity [40]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [40]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Expression [41]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Increases Expression [41]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [42]
Resistin (RETN) OTW5Z1NH RETN_HUMAN Decreases Expression [41]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases ADR [43]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Affects Response To Substance [44]
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⏷ Show the Full List of 20 DOT(s)

References

1 I-COMBINE study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with amlodipine monotherapy in hypertensive patients uncontrolled with amlodipine 5 mg monotherapy: a multicenter, phase III, prospective, randomized, open-label with blinded-end point evaluation study. Clin Ther. 2012 Aug;34(8):1705-19.
2 Irbesartan FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 203534.
4 Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60. Clinical Trial;
5 Amlodipine FDA Label
6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6981).
7 Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
8 Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4.
9 High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
10 Drug interactions with irbesartan. Clin Pharmacokinet. 2001;40(8):605-14.
11 Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
12 Rapid detection of the known SNPs of CYP2C9 using oligonucleotide microarray. World J Gastroenterol. 2003 Jun;9(6):1342-6.
13 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
14 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
15 Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). J Cardiovasc Pharmacol. 2003 Dec;42(6):719-26. doi: 10.1097/00005344-200312000-00005.
16 The mechanism of action of angiotensin II is dependent on direct activation of vascular smooth muscle carbonic anhydrase I. Int J Clin Lab Res. 2000;30(3):119-25. doi: 10.1007/s005990070010.
17 Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists. Hypertension. 1999 Mar;33(3):850-5. doi: 10.1161/01.hyp.33.3.850.
18 Plasma atrial natriuretic peptide in essential hypertension after treatment with irbesartan. Blood Press. 2002;11(2):91-4. doi: 10.1080/08037050211263.
19 Irbesartan inhibits human T-lymphocyte activation through downregulation of activator protein-1. Br J Pharmacol. 2004 Jul;142(6):933-42. doi: 10.1038/sj.bjp.0705785. Epub 2004 Jun 21.
20 Hypotensive shock and angio-oedema from angiotensin II receptor blocker: a class effect in spite of tripled tryptase values. J Intern Med. 2005 Oct;258(4):385-7. doi: 10.1111/j.1365-2796.2005.01547.x.
21 Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J Hypertens. 2002 Apr;20(4):657-63. doi: 10.1097/00004872-200204000-00023.
22 Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy. BMC Cardiovasc Disord. 2003 Sep 18;3:11. doi: 10.1186/1471-2261-3-11. Epub 2003 Sep 18.
23 The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. J Hypertens. 2002 Oct;20(10):2089-93.
24 Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment. BMC Cardiovasc Disord. 2004 Sep 28;4(1):16. doi: 10.1186/1471-2261-4-16.
25 Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Am J Hypertens. 2002 May;15(5):389-93. doi: 10.1016/s0895-7061(02)02256-2.
26 B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J Hypertens. 2003 Mar;21(3):621-4. doi: 10.1097/00004872-200303000-00029.
27 Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients. J Hypertens. 2001 Oct;19(10):1783-7. doi: 10.1097/00004872-200110000-00012.
28 Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 Mar;27(3):169-73. doi: 10.1002/clc.4960270315.
29 Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 May;27(5):287-90. doi: 10.1002/clc.4960270510.
30 A first drug combination for the treatment of arterial hypertension with a calcium channel antagonist (amlodipine besylate) and an angiotensin receptor blocker (valsartan): Exforge. Rev Med Liege. 2007 Nov;62(11):688-94.
31 Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab Dispos. 2014 Feb;42(2):245-9.
32 Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
33 Cell-based high-throughput screening for aromatase inhibitors in the Tox21 10K library. Toxicol Sci. 2015 Oct;147(2):446-57.
34 Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
35 Amlodipine inhibits cell proliferation via PKD1-related pathway. Biochem Biophys Res Commun. 2008 May 2;369(2):376-81. doi: 10.1016/j.bbrc.2008.02.075. Epub 2008 Feb 25.
36 Effects of amlodipine on TGF--induced Smad2, 4 expressions in adriamycin toxicity of rat mesangial cells. Arch Toxicol. 2011 Jun;85(6):663-8. doi: 10.1007/s00204-011-0667-4. Epub 2011 Feb 20.
37 Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension. Int J Cardiol. 2011 Feb 3;146(3):319-25. doi: 10.1016/j.ijcard.2009.07.002. Epub 2009 Aug 3.
38 Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. Ann Med. 2004;36(7):552-7. doi: 10.1080/07853890410017386.
39 Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy. Nephrol Dial Transplant. 2001;16 Suppl 1:114-6. doi: 10.1093/ndt/16.suppl_1.114.
40 G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in human epidermoid carcinoma A431 cells. Biochem Pharmacol. 2007 Apr 1;73(7):943-53. doi: 10.1016/j.bcp.2006.12.011. Epub 2006 Dec 14.
41 Amlodipine improves endothelial function and metabolic parameters in patients with hypertension. Int J Cardiol. 2009 Mar 20;133(1):23-31. doi: 10.1016/j.ijcard.2007.11.058. Epub 2008 Jan 15.
42 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
43 Pharmacogenetic association of the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension. JAMA. 2008 Jan 23;299(3):296-307. doi: 10.1001/jama.299.3.296.
44 Comparing antihypertensive effect and plasma ciclosporin concentration between amlodipine and valsartan regimens in hypertensive renal transplant patients receiving ciclosporin therapy. Am J Cardiovasc Drugs. 2011 Dec 1;11(6):401-9. doi: 10.2165/11593800-000000000-00000.