Details of the Drug

General Information of Drug (ID: DMM4U9G)

Drug Name

R0-93877

Synonyms

Prucalopride; 179474-81-8; UNII-0A09IUW5TP; 4-Amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide; 0A09IUW5TP; C18H26ClN3O3; CHEMBL117287; R-093877; 4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide; R 093877; 4-Amino-5-chloro-N-(1-(3-methoxypropyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-carboxamide; 4-Amino-5-chloro-2,3-dihydro-N-(1-(3-methoxypropyl)-4-piperidyl)-7-benzofurancarboxamide; R093877; Motegrity; Prucalopride [USAN:INN:BAN]

Indication

Disease Entry	ICD 11	Status	REF
Constipation	DD91.1	Approved	[1], [2]
Irritable bowel syndrome	DD91.0	Approved	[3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

367.9

Topological Polar Surface Area (xlogp)

2

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

5

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 64000-762000 mcgday/L [4]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 3800-45000 mcg/L [4]
Bioavailability: The bioavailability of drug is 66% [4]
Clearance: The renal clearance of drug is 17 L/h [5]
Elimination: Prucalopride is mainly excreted by the urine, representing 84% of the administered dose while only 13% of the dose is recovered in feces [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 18 - 20 hours [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.7% [6]
Vd: The volume of distribution (Vd) of drug is 623 L [5]

Chemical Identifiers

Formula: C18H26ClN3O3
IUPAC Name: 4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide
Canonical SMILES: COCCCN1CCC(CC1)NC(=O)C2=CC(=C(C3=C2OCC3)N)Cl
InChI: InChI=1S/C18H26ClN3O3/c1-24-9-2-6-22-7-3-12(4-8-22)21-18(23)14-11-15(19)16(20)13-5-10-25-17(13)14/h11-12H,2-10,20H2,1H3,(H,21,23)
InChIKey: ZPMNHBXQOOVQJL-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3052762
ChEBI ID: CHEBI:135552
CAS Number: 179474-81-8
DrugBank ID: DB06480
TTD ID: D04QSJ
VARIDT ID: DR00187
ACDINA ID: D01369

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 4 receptor (HTR4)	TT07C3Y	5HT4R_HUMAN	Agonist	[7]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Constipation

ICD Disease Classification

DD91.1

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
5-HT 4 receptor (HTR4)	DTT	HTR4	1.70E-02	-0.17	-0.32
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from R0-93877 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of R0-93877 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[24]
Erdafitinib	DMI782S	Moderate	Decreased clearance of R0-93877 due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[25]
Umeclidinium	DM4E8O9	Moderate	Antagonize the effect of R0-93877 when combined with Umeclidinium.	Chronic obstructive pulmonary disease [CA22]	[26]
Revefenacin	DMMP5SI	Moderate	Antagonize the effect of R0-93877 when combined with Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[26]
Levonorgestrel	DM1DP7T	Moderate	Altered absorption of R0-93877 caused by Levonorgestrel.	Contraceptive management [QA21]	[24]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Altered absorption of R0-93877 caused by Oestradiol valerate and dienogest.	Endometriosis [GA10]	[24]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of R0-93877 when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[26]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of R0-93877 due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[27]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of R0-93877 when combined with Methylscopolamine.	Peptic ulcer [DA61]	[26]
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⏷ Show the Full List of 9 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
FD&C blue no. 2	E00446	2723854	Colorant
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Colcothar yellow	E00436	518696	Colorant
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 10 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Prucalopride 2 mg tablet	2 mg	Tablet	Oral
Prucalopride 1 mg tablet	1 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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2	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009175)
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4	Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med. 2017 Feb 23;376(8):717-728. doi: 10.1056/NEJMoa1605767.
5	A Phase I Study to Investigate the Absorption, Pharmacokinetics, and Excretion of [(14)C]Prucalopride After a Single Oral Dose in Healthy Volunteers. Clin Ther. 2016 Sep;38(9):2106-15. doi: 10.1016/j.clinthera.2016.08.003. Epub 2016 Sep 7.
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
8	Resolor, INN-prucalopride
9	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
10	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
11	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
12	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
13	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
14	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
15	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
16	Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5... Endocr Relat Cancer. 2009 Mar;16(1):281-90.
17	Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
18	5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist. J Vet Pharmacol Ther. 2002 Feb;25(1):49-58.
19	The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):125-37.
20	Pharmacology and metabolism of renzapride : a novel therapeutic agent for the potential treatment of irritable bowel syndrome. Drugs R D. 2008;9(1):37-63.
21	The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility. Aliment Pharmacol Ther. 1995 Oct;9(5):563-9.
22	The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties. Front Pharmacol. 2011 May 30;2:25.
23	A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol. 2015 Apr;13(4):701-8.e1.
24	Cerner Multum, Inc. "Australian Product Information.".
25	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
26	EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
27	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.