Details of the Drug Combination

General Information of Drug Combination (ID: DCBAP4Z)

Drug Combination Name
Tadalafil Macitentan
Indication
Disease Entry Status REF
Pulmonary Arterial Hypertension Phase 4 [1]
Component Drugs Tadalafil   DMJZHT1 Macitentan   DMP79A1
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 Tadalafil
Disease Entry ICD 11 Status REF
Benign prostatic hyperplasia GA90 Approved [2]
Erectile dysfunction HA01.1 Approved [3]
Plasma cell myeloma 2A83.1 Approved [2]
Pulmonary hypertension BB01 Approved [2]
Priapism N.A. Investigative [2]
Tadalafil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phosphodiesterase 5A (PDE5A) TTJ0IQB PDE5A_HUMAN Inhibitor [5]
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Tadalafil Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
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Tadalafil Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [7]
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Tadalafil Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A) OTT8Q1AP PDE5A_HUMAN Decreases Activity [8]
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Indication(s) of Macitentan
Disease Entry ICD 11 Status REF
Cardiovascular disease BA00-BE2Z Approved [4]
Macitentan Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Endothelin A receptor (EDNRA) TTKRD0G EDNRA_HUMAN Modulator [9]
Endothelin B receptor (EDNRB) TT3ZTGU EDNRB_HUMAN Modulator [9]
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Macitentan Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [10]
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Macitentan Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Decreases Expression [11]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [11]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Expression [11]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Expression [11]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Pulmonary Arterial Hypertension DCPFSDV N. A. Phase 3 [12]
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References

1 ClinicalTrials.gov (NCT02968901) Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
2 Tadalafil FDA Label
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: 7299).
4 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: 7352).
5 Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
6 In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil. Biol Pharm Bull. 2017;40(8):1314-1319.
7 Contribution of CYP3A isoforms to dealkylation of PDE5 inhibitors: a comparison between sildenafil N-demethylation and tadalafil demethylenation. Biol Pharm Bull. 2015;38(1):58-65.
8 Pharmacotherapy of erectile dysfunction: focus on cardiovascular safety. Expert Opin Drug Saf. 2005 May;4(3):531-40. doi: 10.1517/14740338.4.3.531.
9 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
10 Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects. Clin Pharmacokinet. 2013 Aug;52(8):685-92.
11 From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062.
12 ClinicalTrials.gov (NCT02558231) The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension