Details of the Drug

General Information of Drug (ID: DMMP5SI)

Drug Name
Revefenacin
Synonyms
UNII-G2AE2VE07O; G2AE2VE07O; Revefenacin [INN]; Revefenacin [WHO-DD]; Revefenacin [USAN:INN]; Revefenacin (USAN/INN); SCHEMBL356480; EX-A1722; DB11855; GSK1160724; CS-7743; GSK-1160724; HY-15851; D10978; 1211931-83-7
Indication
Disease Entry ICD 11 Status REF
Chronic obstructive pulmonary disease CA22 Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 597.7
Topological Polar Surface Area (xlogp) 4.1
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 0.03-0.36 mcgh/L [2]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 0.02-0.15 mcg/L [2]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.48-0.51 h [2]
Elimination
27% of drug is excreted in urine, and 54% is excreted in feces [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 22.3 - 70 hours [2]
Metabolism
The drug is metabolized via the lung [2]
Vd
The volume of distribution (Vd) of drug is 218 L [3]
Chemical Identifiers
Formula
C35H43N5O4
IUPAC Name
[1-[2-[[4-[(4-carbamoylpiperidin-1-yl)methyl]benzoyl]-methylamino]ethyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate
Canonical SMILES
CN(CCN1CCC(CC1)OC(=O)NC2=CC=CC=C2C3=CC=CC=C3)C(=O)C4=CC=C(C=C4)CN5CCC(CC5)C(=O)N
InChI
InChI=1S/C35H43N5O4/c1-38(34(42)29-13-11-26(12-14-29)25-40-19-15-28(16-20-40)33(36)41)23-24-39-21-17-30(18-22-39)44-35(43)37-32-10-6-5-9-31(32)27-7-3-2-4-8-27/h2-14,28,30H,15-25H2,1H3,(H2,36,41)(H,37,43)
InChIKey
FYDWDCIFZSGNBU-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11753673
CAS Number
864750-70-9
DrugBank ID
DB11855
TTD ID
D0K1ST
INTEDE ID
DR1412
ACDINA ID
D01385

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Muscarinic acetylcholine receptor (CHRM) TTOXS3C NOUNIPROTAC Antagonist [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6)
Main DME 		DECB0K3 CP2D6_HUMAN Substrate [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Revefenacin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Moderate Accelerated clearance of Revefenacin due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [25]
Ag-221 DMS0ZBI Moderate Decreased clearance of Revefenacin due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [26]
MK-8228 DMOB58Q Moderate Decreased clearance of Revefenacin due to the transporter inhibition by MK-8228. Cytomegaloviral disease [1D82] [27]
Bempedoic acid DM1CI9R Moderate Decreased clearance of Revefenacin due to the transporter inhibition by Bempedoic acid. Hyper-lipoproteinaemia [5C80] [27]
Belladonna DM2RBWK Moderate Additive anticholinergic effects by the combination of Revefenacin and Belladonna. Infectious gastroenteritis/colitis [1A40] [28]
Darolutamide DMV7YFT Moderate Decreased clearance of Revefenacin due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [27]
⏷ Show the Full List of 6 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Kyselina citronova E00014 311 Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Sodium citrate anhydrous E00102 6224 Alkalizing agent; Buffering agent; Complexing agent; Emulsifying agent
Sodium chloride E00077 5234 Diluent; Tonicity agent
Water E00035 962 Solvent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Revefenacin 175 mcg/3 ml solution 175 mcg/3 ml Solution Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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2 A 28-day, randomized, double-blind, placebo-controlled, parallel group study of nebulized revefenacin in patients with chronic obstructive pulmonary disease. Respir Res. 2017 Nov 2;18(1):182. doi: 10.1186/s12931-017-0647-1.
3 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4 A 28-day, randomized, double-blind, placebo-controlled, parallel group study of nebulized revefenacin in patients with chronic obstructive pulmonary disease. Respir Res. 2017 Nov 2;18(1):182.
5 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
6 Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
7 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
8 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
9 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.
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11 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
12 Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
13 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
14 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
15 Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
16 Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.
17 Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):177-84.
18 Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
19 Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7.
20 Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs. Nihon Yakurigaku Zasshi. 1999 Mar;113(3):157-66.
21 Clinical pipeline report, company report or official report of GlaxoSmithKline.
22 The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
23 Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes. Br J Pharmacol. 1987 Apr;90(4):701-7.
24 Long-acting bronchodilators in COPD: Where are we now and where are we going Breathe 06/2014; 10(2):110-120.
25 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
26 Cerner Multum, Inc. "Australian Product Information.".
27 Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
28 Cole JM, Sheehan AH, Jordan JK "Concomitant use of ipratropium and tiotropium in chronic obstructive plmonary disease." Ann Pharmacother 46 (2012): 1717-21. [PMID: 23170031]