General Information of Drug Combination (ID: DCJT0TU)

Drug Combination Name
Dextromethorphan Cerivastatin
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Dextromethorphan   DMUDJZM Cerivastatin   DMXCM7H
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: 2.76
Bliss Independence Score: 2.76
Loewe Additivity Score: 3.35
LHighest Single Agent (HSA) Score: 3.42

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dextromethorphan
Disease Entry ICD 11 Status REF
Allergic rhinitis CA08.0 Approved [2]
Common cold CA00 Approved [2]
Cough MD12 Approved [3]
Fever MG26 Approved [2]
Headache 8A80-8A84 Approved [2]
Rhinitis FA20 Approved [2]
Vasomotor/allergic rhinitis CA08 Approved [2]
Dextromethorphan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor sigma 1 (OPRS1) TT5TPI6 SGMR1_HUMAN Agonist [7]
------------------------------------------------------------------------------------
Dextromethorphan Interacts with 10 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [11]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [12]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [12]
Cholesterol 24-hydroxylase (CYP46A1) DEKP5HX CP46A_HUMAN Metabolism [14]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [15]
Cytochrome P450 130A1 (cyp130) DE6CQ0I CP130_MYCTU Metabolism [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 DME(s)
Dextromethorphan Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Methylation [17]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Methylation [17]
Cholesterol 24-hydroxylase (CYP46A1) OTJ27FOX CP46A_HUMAN Decreases Methylation [14]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases Response To Substance [18]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [19]
Beta-hexosaminidase subunit beta (HEXB) OTROYLCR HEXB_HUMAN Increases Secretion [19]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [19]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [19]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [20]
Mas-related G-protein coupled receptor member X2 (MRGPRX2) OT2XA799 MRGX2_HUMAN Affects Binding [19]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Affects Metabolism [6]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Affects Metabolism [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 DOT(s)
Indication(s) of Cerivastatin
Disease Entry ICD 11 Status REF
Hyperlipidaemia 5C80 Approved [4]
Multiple myeloma 2A83 Phase 1/2 [5]
Cerivastatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [5]
------------------------------------------------------------------------------------
Cerivastatin Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [21]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [21]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [22]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [23]
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DT56EKP NTCP_HUMAN Substrate [24]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [23]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [25]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DTP(s)
Cerivastatin Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [26]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [27]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [28]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [28]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [29]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [27]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DME(s)
Cerivastatin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases ADR [30]
------------------------------------------------------------------------------------

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 Dextromethorphan 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: 6953).
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: 2950).
5 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
6 Comparison of various urine collection intervals for caffeine and dextromethorphan phenotyping in children. J Clin Pharmacol. 2004 Jul;44(7):708-14. doi: 10.1177/0091270004266624.
7 Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6 inhibitor, quinidine/dextromethorphan. Drugs R D. 2005;6(3):174-7.
8 Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? Drug Metab Dispos. 2001 Nov;29(11):1514-20.
9 Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723.
10 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
11 Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol. 1994 Jul 5;48(1):173-82.
12 Multiple human cytochromes contribute to biotransformation of dextromethorphan in-vitro: role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. J Pharm Pharmacol. 1998 Sep;50(9):997-1004.
13 Enzymes in addition to CYP3A4 and 3A5 mediate N-demethylation of dextromethorphan in human liver microsomes. Biopharm Drug Dispos. 1999 Oct;20(7):341-6.
14 Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
15 The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
16 Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets? Appl Microbiol Biotechnol. 2019 May;103(9):3597-3614.
17 Evidence of significant contribution from CYP3A5 to hepatic drug metabolism. Drug Metab Dispos. 2004 Dec;32(12):1434-45. doi: 10.1124/dmd.104.001313. Epub 2004 Sep 21.
18 Myoclonus after dextromethorphan administration in peritoneal dialysis. Ann Pharmacother. 2011 Jan;45(1):e1. doi: 10.1345/aph.1P301. Epub 2010 Dec 14.
19 Dextromethorphan - A widely-used cough suppressant - Induces local anaphylaxis via MRGPRX2 on mast cells. Chem Biol Interact. 2020 Oct 1;330:109248. doi: 10.1016/j.cbi.2020.109248. Epub 2020 Aug 29.
20 Effects of common antitussive drugs on the hERG potassium channel current. J Cardiovasc Pharmacol. 2008 Dec;52(6):494-9. doi: 10.1097/FJC.0b013e31818eec8d.
21 Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther. 2005 Sep;314(3):1059-67.
22 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
23 FDA Drug Development and Drug Interactions
24 Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica. 2011 Jan;41(1):24-34.
25 pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
26 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.
27 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
28 Drug Interactions Flockhart Table
29 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
30 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.