Details of the Drug Combination

General Information of Drug Combination (ID: DCJNGYI)

• Drug Combination Name: Ipratropium + Salbutamol
• Indication: Asthma; Status: Phase 1 [1]
• Component Drugs:
  Ipratropium (DMFQ320): Small molecular drug
  Salbutamol (DMN9CWF): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ipratropium

Disease Entry	ICD 11	Status	REF
Obstructive lung disease	CA22.Z	Approved	[2]

Ipratropium Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Modulator	[6]

Ipratropium Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[8]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[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	[7]

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	[10]
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Metabolism	[11]
Sulfotransferase 1A3 (SULT1A3)	DEP7E8X	ST1A3_HUMAN	Metabolism	[12]

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	[13]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[14]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[15]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[16]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[17]
Creatine kinase M-type (CKM)	OTME0KO7	KCRM_HUMAN	Increases Secretion	[18]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[16]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Asthma	DCPAUFA	N. A.	Approved	[19]
Asthma	DCO576V	N. A.	Phase 4	[20]

References

• [1] ClinicalTrials.gov (NCT05550402) Role of Parasympathetic Activity in Mild to Severe Asthma With Fixed Airway Obstruction (PARASMA Study)
• [2] 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: 325).
• [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] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [7] 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.
• [8] Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95.
• [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] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169. (ID: O95477)
• [20] ClinicalTrials.gov (NCT02235428) Study to Assess the Efficacy of Ipratropium Bromide Associated With High Dose Salbutamol by Repeated Nebulisation Versus Repeat Nebulisation of Salbutamol Alone, in Acute Asthmatic Attacks in Young Children