Details of the Drug Combination

General Information of Drug Combination (ID: DCJWETV)

• Drug Combination Name: Glycopyrrolate + Salbutamol
• Indication: Asthma; Status: Phase 3 [1]
• Component Drugs:
  Glycopyrrolate (DM2M3ZA): Small molecular drug
  Salbutamol (DMN9CWF): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Glycopyrrolate

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[2]
Chronic obstructive pulmonary disease	CA22	Approved	[3]

Glycopyrrolate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M1 (CHRM1)	TTZ9SOR	ACM1_HUMAN	Antagonist	[7]

Glycopyrrolate 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	[8]

Indication(s) of Salbutamol

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[4]
Adult respiratory distress syndrome	CB00	Approved	[5]
Severe asthma	CA23	Approved	[6]

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	[8]

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 24 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]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Increases Expression	[14]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[15]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[16]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Increases Expression	[17]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Decreases Expression	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[18]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Decreases Expression	[18]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[19]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[20]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[21]
Creatine kinase M-type (CKM)	OTME0KO7	KCRM_HUMAN	Increases Secretion	[22]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[19]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Increases Expression	[20]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Expression	[20]
Platelet-activating factor receptor (PTAFR)	OT2133DF	PTAFR_HUMAN	Increases Expression	[20]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[20]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Decreases Activity	[23]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[18]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[19]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[18]
Hepatic sodium/bile acid cotransporter (SLC10A1)	OTUJVMCL	NTCP_HUMAN	Increases Expression	[15]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[18]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Affects Response To Substance	[24]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Chronic Obstructive Pulmonary Disease	DCWDUM9	N. A.	Phase 1	[25]

References

• [1] ClinicalTrials.gov (NCT02127697) Study of Efficacy and Safety of NVA237 in Patients With Poorly Controlled Asthma
• [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: 7459).
• [3] Clinical pipeline report, company report or official report of Novartis.
• [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: 558).
• [5] Effects of nebulized salbutamol on respiratory mechanics in adult respiratory distress syndrome. Intensive Care Med. 1997 Jan;23(1):58-64.
• [6] 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.
• [7] Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. Clin Pharmacol Ther. 2008 May;83(5):692-701.
• [8] 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.
• [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] Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds. Toxicol Appl Pharmacol. 2007 Dec 1;225(2):142-53.
• [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] A prospective study of the effects of prolonged timolol therapy on alpha- and beta-adrenoceptor and angiotensin II receptor mediated responses in normal subjects. Br J Clin Pharmacol. 1997 Mar;43(3):301-8. doi: 10.1111/j.1365-2125.1997.00559.x.
• [18] 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.
• [19] [Role of salbutamol in inducing apoptosis of cultured human airway smooth muscle cells]. Zhonghua Jie He He Hu Xi Za Zhi. 2001 Apr;24(4):219-24.
• [20] Mechanisms by which S-albuterol induces human bronchial smooth muscle cell proliferation. Int Arch Allergy Immunol. 2008;146(4):321-33. doi: 10.1159/000121466. Epub 2008 Mar 21.
• [21] 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.
• [22] 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.
• [23] Association of human serum paraoxonase-1 with some respiratory drugs. J Biochem Mol Toxicol. 2019 Dec;33(12):e22407. doi: 10.1002/jbt.22407. Epub 2019 Oct 3.
• [24] Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment. BMC Cardiovasc Disord. 2004 Sep 28;4(1):16. doi: 10.1186/1471-2261-4-16.
• [25] ClinicalTrials.gov (NCT01120691) Effect of QVA149 Versus NVA237 and Tiotropium on Chronic Obstructive Pulmonary Disorder (COPD) Exacerbations