Details of the Drug Combination

General Information of Drug Combination (ID: DC9WTUP)

• Drug Combination Name: Brilinta + Rosuvastatin
• Indication: Pharmacokinetics; Status: Phase 1 [1]
• Component Drugs:
  Brilinta (DMBR01X): Small molecular drug
  Rosuvastatin (DMMIQ7G): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Brilinta

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[2]
Thrombosis	DB61-GB90	Approved	[3]
Arterial thrombosis	DB61-DD30	Phase 3	[4]
Myocardial infarction	BA41-BA43	Phase 3	[4]
Peripheral vascular disease	BD4Z	Investigative	[5]

Brilinta Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
P2Y purinoceptor 12 (P2RY12)	TTZ1DT0	P2Y12_HUMAN	Antagonist	[9]

Brilinta Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

Brilinta Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]

Brilinta Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Terminal nucleotidyltransferase 4A (TENT4A)	OT0G3KR0	PAPD7_HUMAN	Increases ADR	[12]
CD9 antigen (CD9)	OT2184XU	CD9_HUMAN	Increases ADR	[12]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases ADR	[12]
Aryl-hydrocarbon-interacting protein-like 1 (AIPL1)	OT4VBD78	AIPL1_HUMAN	Increases ADR	[13]
Actin-related protein 2/3 complex subunit 1A (ARPC1A)	OTAEEXGQ	ARC1A_HUMAN	Increases ADR	[8]
Putative protein CASTOR3P (GATS)	OTDYE3XK	CAST3_HUMAN	Increases ADR	[8]
LIM domain kinase 2 (LIMK2)	OTRJD7VZ	LIMK2_HUMAN	Increases ADR	[12]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases ADR	[8]

Indication(s) of Rosuvastatin

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Approved	[6]
Hypercholesterolaemia	5C80.0	Approved	[7]
Hyperlipidemia, familial combined, LPL related	N.A.	Approved	[6]
Hypertriglyceridemia	5C80.1	Approved	[6]
Elevated C-reactive protein	MA14.15	Phase 3	[7]
Colon cancer	2B90.Z	Investigative	[6]
Precancerous condition	N.A.	Investigative	[6]
Stroke	8B20	Investigative	[6]

Rosuvastatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[14]

Rosuvastatin Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[15]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[15]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[15]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[16]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[17]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[16]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[15]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[15]

Rosuvastatin Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[18]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[18]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[19]

Rosuvastatin Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases ADR	[20]
Kinesin-like protein KIF6 (KIF6)	OTDH3MR4	KIF6_HUMAN	Increases ADR	[21]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases ADR	[22]

References

• [1] ClinicalTrials.gov (NCT05373277) KF2019#1-trial: Effects of a Thrombocyte Inhibitor on a Cholesterol-lowering Drug
• [2] Ticagrelor-Induced Syncope/Bradyarrhythmia. Cureus. 2021 Jan 23;13(1):e12874.
• [3] 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: 1765).
• [4] ClinicalTrials.gov (NCT01732822) A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease. U.S. National Institutes of Health.
• [5] Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis. Drugs. 2022 Aug;82(12):1287-1302.
• [6] Rosuvastatin FDA Label
• [7] 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: 2954).
• [8] Effect of genetic variations on ticagrelor plasma levels and clinical outcomes. Eur Heart J. 2015 Aug 1;36(29):1901-12.
• [9] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [10] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [11] Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010 Sep;38(9):1514-21.
• [12] Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. J Med Genet. 2013 Sep;50(9):599-605. doi: 10.1136/jmedgenet-2012-101466. Epub 2013 Jun 17.
• [13] Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy. Clin Cancer Res. 2015 Oct 1;21(19):4337-46. doi: 10.1158/1078-0432.CCR-15-0133. Epub 2015 May 26.
• [14] New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
• [15] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
• [16] Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
• [17] The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
• [18] Effects of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharm Res. 2006 Mar;23(3):506-12.
• [19] Pharmacokinetics of rosuvastatin when coadministered with rifampicin in healthy males: a randomized, single-blind, placebo-controlled, crossover study. Clin Ther. 2008 Jul;30(7):1283-9.
• [20] ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin. Clin Pharmacol Ther. 2010 May;87(5):558-62.
• [21] Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol. 2008 Jan 29;51(4):435-43. doi: 10.1016/j.jacc.2007.05.057.
• [22] Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004 Jun 16;291(23):2821-7. doi: 10.1001/jama.291.23.2821.