General Information of Drug Combination (ID: DC1K4YQ)

Drug Combination Name
Tolvaptan Primidone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Tolvaptan   DMIWFRL Primidone   DM0WX6I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 0.54
Bliss Independence Score: 0.54
Loewe Additivity Score: 14.25
LHighest Single Agent (HSA) Score: 14.26

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Tolvaptan
Disease Entry ICD 11 Status REF
Autosomal dominant polycystic kidney disease GB81 Approved [2]
Hyponatraemia 5C72 Approved [3]
Heart failure BD10-BD13 Phase 3 [3]
Hypernatremia 5C71 Investigative [2]
Tolvaptan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vasopressin V2 receptor (V2R) TTK8R02 V2R_HUMAN Antagonist [6]
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Tolvaptan Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Tolvaptan Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
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Tolvaptan Interacts with 7 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 Activity [9]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Activity [9]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [9]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [10]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Activity [9]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [10]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Activity [9]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Primidone
Disease Entry ICD 11 Status REF
Epilepsy 8A60-8A68 Approved [4]
Epilepsy with generalized tonic-clonic seizures N.A. Approved [5]
Focal epilepsy N.A. Approved [5]
Primidone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
GABA(A) receptor alpha-1 (GABRA1) TT1MPAY GBRA1_HUMAN Antagonist [11]
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Primidone Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [12]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [13]
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Primidone Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases ADR [14]
Serum paraoxonase/arylesterase 1 (PON1) OTD0Z2XO PON1_HUMAN Decreases Activity [15]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [16]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [17]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Decreases Expression [17]
Protein S100-A8 (S100A8) OTVMOB3F S10A8_HUMAN Increases Expression [18]
Protein S100-A9 (S100A9) OTOARHCS S10A9_HUMAN Increases Expression [18]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [19]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [17]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Increases ADR [14]
Glutathione hydrolase 7 (GGT7) OTW4IO3I GGT7_HUMAN Increases ADR [14]
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⏷ Show the Full List of 11 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Tolvaptan 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: 2226).
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: 5338).
5 Primidone FDA Label
6 Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
7 In vitro P-glycoprotein interactions and steady-state pharmacokinetic interactions between tolvaptan and digoxin in healthy subjects. J Clin Pharmacol. 2011 May;51(5):761-9.
8 Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88.
9 Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury?. Toxicol Sci. 2016 Jan;149(1):237-50. doi: 10.1093/toxsci/kfv231. Epub 2015 Oct 26.
10 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.
11 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
12 Prescribrt's digital referenve - Primidone - Drug Summary.
13 Clinically significant pharmacokinetic drug interactions between antiepileptic drugs. J Clin Pharm Ther. 1999 Apr;24(2):87-92.
14 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
15 Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
16 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
17 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
18 Prediction of drug-induced liver injury using keratinocytes. J Appl Toxicol. 2017 Jul;37(7):863-872. doi: 10.1002/jat.3435. Epub 2017 Jan 31.
19 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.