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]
Irritable bowel syndrome	DD91.0	Approved	[2]

• Affected Organisms: Humans and other mammals
• ATC Code:
  A06AX05: R0-93877
  A06AX: Other drugs for constipation
  A06A: DRUGS FOR CONSTIPATION
  A06: DRUGS FOR CONSTIPATION
  A: ALIMENTARY TRACT AND METABOLISM
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 367.9
  Logarithm of the Partition Coefficient (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 [3]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 3800-45000 mcg/L [3]
  Bioavailability: The bioavailability of drug is 66% [3]
  Clearance: The renal clearance of drug is 17 L/h [4]
  Elimination: Prucalopride is mainly excreted by the urine, representing 84% of the administered dose while only 13% of the dose is recovered in feces [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 18 - 20 hours [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.7% [5]
  Vd: The volume of distribution (Vd) of drug is 623 L [4]
• 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: CHEMBL117287
  CAS Number: 179474-81-8
  UNII: 0A09IUW5TP
  DrugBank ID: DB06480
  TTD ID: D04QSJ
  VARIDT ID: DR00187
  ACDINA ID: D01369
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug

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	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

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

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	DMTI0ZO	Moderate	Decreased clearance of R0-93877 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[8]
Erdafitinib	DMI782S	Moderate	Decreased clearance of R0-93877 due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[9]
Umeclidinium	DM4E8O9	Moderate	Antagonize the effect of R0-93877 when combined with Umeclidinium.	Chronic obstructive pulmonary disease [CA22]	[10]
Revefenacin	DMMP5SI	Moderate	Antagonize the effect of R0-93877 when combined with Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[10]
Levonorgestrel	DM1DP7T	Moderate	Altered absorption of R0-93877 caused by Levonorgestrel.	Contraceptive management [QA21]	[8]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Altered absorption of R0-93877 caused by Oestradiol valerate and dienogest.	Endometriosis [GA10]	[8]
Belladonna	DM2RBWK	Moderate	Antagonize the effect of R0-93877 when combined with Belladonna.	Infectious gastroenteritis/colitis [1A40]	[10]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of R0-93877 due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[11]
Methylscopolamine	DM5VWOB	Moderate	Antagonize the effect of R0-93877 when combined with Methylscopolamine.	Peptic ulcer [DA61]	[10]

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

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

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [3] Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med. 2017 Feb 23;376(8):717-728. doi: 10.1056/NEJMoa1605767.
• [4] 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.
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [7] Resolor, INN-prucalopride
• [8] Cerner Multum, Inc. "Australian Product Information.".
• [9] Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
• [10] EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
• [11] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.