Details of the Drug Combination

General Information of Drug Combination (ID: DC2UGBT)

• Drug Combination Name: Oxycodone + Lansoprazole
• Indication: Pain, Fracture, Sprain; Status: Phase 1 [1]
• Component Drugs:
  Oxycodone (DMXLKHV): Small molecular drug
  Lansoprazole (DMXYLQ3): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Oxycodone

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[2]
Pain	MG30-MG3Z	Approved	[3]
Back pain	ME84.Z	Phase 3	[4]

Oxycodone Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Modulator	[6]
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Agonist	[7]

Oxycodone Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[8]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[8]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[8]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Affects Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Response To Substance	[10]

Indication(s) of Lansoprazole

Disease Entry	ICD 11	Status	REF
Gastric ulcer	DA60	Approved	[5]
Gastrinoma	2C10.1	Approved	[5]
Peptic ulcer	DA61	Approved	[5]

Lansoprazole Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[12]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[13]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[15]

Lansoprazole Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[16]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Hydroxylation	[17]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Increases Hydroxylation	[13]
Cytochrome P450 2C18 (CYP2C18)	OTY687L9	CP2CI_HUMAN	Increases Hydroxylation	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Response To Substance	[18]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[16]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[19]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Increases Expression	[19]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[20]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[21]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Expression	[22]
Protransforming growth factor alpha (TGFA)	OTPD1LL9	TGFA_HUMAN	Increases Expression	[22]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[23]
Gastrin (GAST)	OTD0IP9N	GAST_HUMAN	Increases Expression	[24]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Increases Expression	[21]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Decreases Expression	[22]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[25]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[26]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Affects Binding	[27]
Oxysterols receptor LXR-beta (NR1H2)	OT4APA60	NR1H2_HUMAN	Increases Activity	[21]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Increases Expression	[28]
Oxysterols receptor LXR-alpha (NR1H3)	OT54YZ9I	NR1H3_HUMAN	Increases Activity	[21]
Phosphoethanolamine/phosphocholine phosphatase (PHOSPHO1)	OT43A0JA	PHOP1_HUMAN	Decreases Activity	[29]
Fibroblast growth factor 21 (FGF21)	OT3RXVRD	FGF21_HUMAN	Increases Expression	[30]

References

• [1] ClinicalTrials.gov (NCT00685295) Fentanyl Administered Intraorally for Rapid Treatment of Orthopedic Pain
• [2] Oxycodone 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: 7093).
• [4] ClinicalTrials.gov (NCT01427283) A Study of Oxycodone/Naloxone Controlled-release Tablets (OXN) to Assess Analgesic Efficacy and Management of Opioid-induced Constipation (OIC) in Opioid-experienced Subjects With Moderate to Severe Chronic Low Back Pain. U.S. National Institutes of Health.
• [5] Lansoprazole 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. (Target id: 319).
• [7] Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
• [8] Chronic oxycodone induces integrated stress response in rat brain. BMC Neurosci. 2015 Sep 16;16:58. doi: 10.1186/s12868-015-0197-8.
• [9] Evaluation of Recombinant CYP3A4 Variants on the Metabolism of Oxycodone In Vitro. Chem Res Toxicol. 2021 Jan 18;34(1):103-109. doi: 10.1021/acs.chemrestox.0c00361. Epub 2021 Jan 4.
• [10] Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol. 2010 Jun;160(4):919-30. doi: 10.1111/j.1476-5381.2010.00709.x.
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• [14] 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.
• [15] Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes. Br J Clin Pharmacol. 2005 Mar;59(3):302-9.
• [16] Measurement of cytochrome P450 gene induction in human hepatocytes using quantitative real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos. 2000 Jul;28(7):781-8.
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• [18] Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects. Eur J Clin Pharmacol. 2009 Jun;65(6):593-600. doi: 10.1007/s00228-009-0625-8. Epub 2009 Feb 24.
• [19] Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics. Xenobiotica. 2003 Feb;33(2):107-18.
• [20] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [21] Proton pump inhibitor lansoprazole is a nuclear liver X receptor agonist. Biochem Pharmacol. 2010 May 1;79(9):1310-6. doi: 10.1016/j.bcp.2009.12.018. Epub 2010 Jan 8.
• [22] Effect of chronic duodenal ulceration and its treatment with lanzoprazole or sucralfate on gastroduodenal mucosal protein turnover and TGF-alpha, bFGF, and EGF receptor expression in humans. Dig Dis Sci. 1998 Dec;43(12):2764-70. doi: 10.1023/a:1026680017329.
• [23] Comparison of the effects of proton pump inhibitors on human plasma adrenocorticotropic hormone and cortisol levels under the starved condition. Biomed Pharmacother. 2006 Apr;60(3):109-12. doi: 10.1016/j.biopha.2006.01.004. Epub 2006 Feb 21.
• [24] Influence of lansoprazole on intragastric 24-hour pH, meal-stimulated gastric acid secretion, and concentrations of gastrointestinal hormones and enzymes in serum and gastric juice in healthy volunteers. Digestion. 1995;56(2):137-44. doi: 10.1159/000201233.
• [25] Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. Biochem Biophys Res Commun. 2006 Jul 7;345(3):1014-21. doi: 10.1016/j.bbrc.2006.04.170. Epub 2006 May 6.
• [26] Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease. Am J Gastroenterol. 2004 Apr;99(4):589-97. doi: 10.1111/j.1572-0241.2004.04110.x.
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• [28] Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020 Jan;318:86-91. doi: 10.1016/j.toxlet.2019.10.016. Epub 2019 Oct 24.
• [29] Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization. J Bone Miner Res. 2007 Apr;22(4):617-27. doi: 10.1359/jbmr.070108.
• [30] Increased immunoreactivity and concentration of basic fibroblast growth factor in lansoprazole-treated gastric mucosa. J Clin Gastroenterol. 1995;21 Suppl 1:S24-9.