Details of the Drug Combination

General Information of Drug Combination (ID: DCLUY6J)

• Drug Combination Name: Fluticasone + Salbutamol
• Indication: Asthma; Status: Phase 4 [1]
• Component Drugs:
  Fluticasone (DMGCSVF): Small molecular drug
  Salbutamol (DMN9CWF): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fluticasone

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[2]

Fluticasone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Antagonist	[6]

Fluticasone Interacts with 3 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]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[8]

Indication(s) of Salbutamol

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[3]
Adult respiratory distress syndrome	CB00	Approved	[4]
Severe asthma	CA23	Approved	[5]

Salbutamol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-2 (ADRB2)	TT2CJVK	ADRB2_HUMAN	Agonist	[9]

Salbutamol Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]

Salbutamol Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Metabolism	[12]
Sulfotransferase 1A3 (SULT1A3)	DEP7E8X	ST1A3_HUMAN	Metabolism	[13]

Salbutamol Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Decreases Response To Substance	[14]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[15]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[16]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[17]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[18]
Creatine kinase M-type (CKM)	OTME0KO7	KCRM_HUMAN	Increases Secretion	[19]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[17]

References

• [1] ClinicalTrials.gov (NCT03363191) The Efficacy of Fluticasone Furoate/Vilanterol Versus (vs) Fluticasone Furoate on Asthma
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 558).
• [4] Effects of nebulized salbutamol on respiratory mechanics in adult respiratory distress syndrome. Intensive Care Med. 1997 Jan;23(1):58-64.
• [5] Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial. Pediatr Pulmonol. 2019 Apr;54(4):372-377.
• [6] Fluticasone furoate nasal spray in allergic rhinitis. Drugs Today (Barc). 2008 Apr;44(4):251-60.
• [7] Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35.
• [8] Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40.
• [9] Potential of beta2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol). CNS Drugs. 2002;16(1):1-8.
• [10] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [11] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [12] Effect of carboxylesterase 1 c.428G>A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015 Nov;80(5):1131-8.
• [13] SULT 1A3 single-nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: are some athletes at risk of higher urine levels? Drug Test Anal. 2015 Feb;7(2):109-13.
• [14] beta2-adrenergic receptor polymorphisms and salbutamol-stimulated energy expenditure. J Clin Endocrinol Metab. 2005 Apr;90(4):2301-7. doi: 10.1210/jc.2004-1356. Epub 2005 Feb 1.
• [15] Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis. Toxicol Sci. 2023 Nov 28;196(2):200-217. doi: 10.1093/toxsci/kfad088.
• [16] Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: a placebo-controlled dose-response study in healthy volunteers. Br J Clin Pharmacol. 1987 Nov;24(5):645-53. doi: 10.1111/j.1365-2125.1987.tb03224.x.
• [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] Levalbuterol inhibits human airway smooth muscle cell proliferation: therapeutic implications in the management of asthma. Int Arch Allergy Immunol. 2006;139(3):225-36. doi: 10.1159/000091168. Epub 2006 Jan 27.
• [19] Elevation of creatine kinase from skeletal muscle associated with inhaled albuterol. Ann Allergy Asthma Immunol. 1996 Dec;77(6):488-90. doi: 10.1016/S1081-1206(10)63356-X.