ELUXADOLINE DIHYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H35N5O5.2ClH
Molecular Weight	642.573
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of ELUXADOLINE DIHYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.COC1=CC=C(CN([C@@H](C)C2=NC(=CN2)C3=CC=CC=C3)C(=O)[C@@H](N)CC4=C(C)C=C(C=C4C)C(N)=O)C=C1C(O)=O

InChI

InChIKey=YFUUQKJOCLQHMZ-ISJKLOBTSA-N

InChI=1S/C32H35N5O5.2ClH/c1-18-12-23(29(34)38)13-19(2)24(18)15-26(33)31(39)37(17-21-10-11-28(42-4)25(14-21)32(40)41)20(3)30-35-16-27(36-30)22-8-6-5-7-9-22;;/h5-14,16,20,26H,15,17,33H2,1-4H3,(H2,34,38)(H,35,36)(H,40,41);2*1H/t20-,26-;;/m0../s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940s000lbl.pdf
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800031329 | https://www.ncbi.nlm.nih.gov/pubmed/22695132 | https://www.ncbi.nlm.nih.gov/pubmed/25261794

Eluxadoline, an orally active mixed μ opioid receptor (μOR) agonist δ opioid receptor (δOR) antagonist. Eluxadoline normalizes gastrointestinal (GI) transit and defecation under conditions of novel environment stress or post-inflammatory altered GI function. Allergan (previously Actavis) is developing eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome. The agent was originated by Janssen Pharmaceutica. Eluxadoline has been launched in the US under trade name VIBERZI (eluxadoline) tablets, while is at the preregistration stage in the EU.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25261794 \| https://www.ncbi.nlm.nih.gov/pubmed/22671931 \| https://www.ncbi.nlm.nih.gov/pubmed/22695132	Agonist 2678		1.7 nM [Ki]
Delta opioid receptor 77 Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25261794 \| https://www.ncbi.nlm.nih.gov/pubmed/22671931 \| https://www.ncbi.nlm.nih.gov/pubmed/22695132	Antagonist 2778		1.3 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Irritable bowel syndrome with diarrhea 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940s000lbl.pdf	Primary		Approved 8429	VIBERZI Approved Use VIBERZI is a mu-opioid receptor agonist, indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D) Launch Date 2015

C_max

Value	Dose	Analyte	Population
29.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
58.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
104.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
237.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
268.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
21.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719721	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ELUXADOLINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
19% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206940s007lbl.pdf	unknown, oral		ELUXADOLINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2000 mg 1 times / day single, oral Highest studied dose Dose: 2000 mg, 1 times / day Route: oral Route: single Dose: 2000 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf https://www.ema.europa.eu/en/documents/assessment-report/truberzi-epar-public-assessment-report_en.pdf	healthy, adult Health Status: healthy Age Group: adult Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf https://www.ema.europa.eu/en/documents/assessment-report/truberzi-epar-public-assessment-report_en.pdf	Other AEs: Nausea, Abdominal pain... Other AEs: Nausea Abdominal pain Constipation Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf https://www.ema.europa.eu/en/documents/assessment-report/truberzi-epar-public-assessment-report_en.pdf
1000 mg 1 times / day single, oral MTD Dose: 1000 mg, 1 times / day Route: oral Route: single Dose: 1000 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf https://www.ema.europa.eu/en/documents/assessment-report/truberzi-epar-public-assessment-report_en.pdf	healthy, adult n = 8 Health Status: healthy Age Group: adult Sex: F Population Size: 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf https://www.ema.europa.eu/en/documents/assessment-report/truberzi-epar-public-assessment-report_en.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf https://www.ema.europa.eu/en/documents/assessment-report/truberzi-epar-public-assessment-report_en.pdf
1500 mg 1 times / day single, oral MTD Dose: 1500 mg, 1 times / day Route: oral Route: single Dose: 1500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf	healthy, adult n = 5 Health Status: healthy Age Group: adult Sex: M Population Size: 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf
100 mg 2 times / day multiple, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940Orig1s000lbl.pdf	unhealthy, mean age 45.5 years n = 1032 Health Status: unhealthy Condition: irritable bowel syndrome with diarrhea Age Group: mean age 45.5 years Sex: M+F Population Size: 1032 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940Orig1s000lbl.pdf	Other AEs: Rash... Other AEs: Rash (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940Orig1s000lbl.pdf
100 mg 2 times / day multiple, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf	unhealthy, mean age 45.5 years n = 1032 Health Status: unhealthy Condition: irritable bowel syndrome with diarrhea Age Group: mean age 45.5 years Sex: M+F Population Size: 1032 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf	Disc. AE: Abdominal pain, Constipation... Other AEs: Dizziness, Fatigue... AEs leading to discontinuation/dose reduction: Abdominal pain (1.4%) Constipation (1.5%) Headache (0.1%) Dizziness (0.1%) Vomiting (0.2%) Somnolence (0.1%) Other AEs: Dizziness (2.6%) Fatigue (1.9%) Anxiety (1.9%) Depression (1.2%) Somnolence (1.1%) Nausea (7.1%) Constipation (8.1%) Abdominal pain (4.6%) Vomiting (4.2%) Flatulence (3.2%) Abdominal distension (2.7%) Upper respiratory tract infection (5.1%) Nasopharyngitis (3%) Sinusitis (2.6%) Bronchitis (2.9%) Gastroenteritis viral (1.4%) Urinary tract infection (1.7%) Headache (4.3%) Dizziness (3.2%) Fatigue (1.9%) ALT increased (2.5%) Hypertension (1.4%) Bilirubin elevated (1.3%) Alkaline phosphatase (0.8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf
75 mg 2 times / day multiple, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: multiple Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940Orig1s000lbl.pdf	unhealthy, mean age 45.5 years n = 807 Health Status: unhealthy Condition: irritable bowel syndrome with diarrhea Age Group: mean age 45.5 years Sex: M+F Population Size: 807 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940Orig1s000lbl.pdf	Other AEs: Rash... Other AEs: Rash (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206940Orig1s000lbl.pdf
75 mg 2 times / day multiple, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: multiple Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf	unhealthy, mean age 45.5 years n = 807 Health Status: unhealthy Condition: irritable bowel syndrome with diarrhea Age Group: mean age 45.5 years Sex: M+F Population Size: 807 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf	Disc. AE: Abdominal pain, Constipation... Other AEs: Dizziness, Fatigue... AEs leading to discontinuation/dose reduction: Abdominal pain (1.5%) Constipation (1.1%) Nausea (0.6%) Headache (0.4%) Dizziness (0.1%) Vomiting (0.1%) Pruritis (0.1%) Other AEs: Dizziness (2.6%) Fatigue (2.6%) Anxiety (1.2%) Depression (1.1%) Somnolence (0.1%) Nausea (8.1%) Constipation (7.4%) Abdominal pain (4.1%) Vomiting (4%) Flatulence (2.6%) Abdominal distension (2.6%) Upper respiratory tract infection (3.3%) Nasopharyngitis (4.1%) Sinusitis (3.3%) Bronchitis (3.2%) Gastroenteritis viral (2.7%) Urinary tract infection (2.1%) Headache (4%) Dizziness (2.6%) Fatigue (2.6%) ALT increased (2.1%) Hypertension (2.5%) Bilirubin elevated (1.9%) Alkaline phosphatase (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf
200 mg 2 times / day multiple, oral Studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf Page: nda/2015/206940Orig1s000MedR.pdf - p.3	unhealthy, mean age 63.6 years n = 171 Health Status: unhealthy Condition: irritable bowel syndrome with diarrhea Age Group: mean age 63.6 years Sex: M+F Population Size: 171 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf Page: nda/2015/206940Orig1s000MedR.pdf - p.3	Disc. AE: Abdominal pain, Constipation... AEs leading to discontinuation/dose reduction: Abdominal pain (7%) Constipation (2.3%) Nausea (2.3%) Headache (1.8%) Dizziness (1.8%) Vomiting (1.2%) Fatigue (1.2%) Dry mouth (1.8%) Somnolence (1.2%) Pruritis (1.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000MedR.pdf Page: nda/2015/206940Orig1s000MedR.pdf - p.3

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 OATP1B1 788 OAT1 599 OAT3 642 OCT1 512 OCT2 647 OATP1B3 706 P-gp 1461 BCRP 699 BSEP 402 MRP2 383 CYP2A6 707 CYP2B6 810 CYP2E1 882	OAT3 339 OATP1B1 406 BSEP 52 MRP2 205 OCT1 327 OCT2 355 OAT1 326 OATP1B3 350 P-gp 1537 BCRP 561 UGT1A1 418	CYP1A2 701 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	weak
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	weak
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	weak
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	yes
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes	yes (co-administration study) Comment: Coadministration of single oral dose of 500 mg probenecid (an inhibitor of MRP2 and OAT3) with single oral dose of 100 mg eluxadoline increased both AUC and Cmax of eluxadoline by 30%, which is not considered to be clinically significant. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes	yes (co-administration study) Comment: Coadministration of single oral dose of 500 mg probenecid (an inhibitor of MRP2 and OAT3) with single oral dose of 100 mg eluxadoline increased both AUC and Cmax of eluxadoline by 30%, which is not considered to be clinically significant. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes	yes (co-administration study) Comment: Coadministration of single oral dose of 600 mg cyclosporine (an inhibitor of many transporters including OATP1B1 and MRP2) with single oral dose of 100 mg eluxadoline increased eluxadoline AUC by 4.4 fold and Cmax by 6.2 fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000ClinPharmR.pdf#page=10 Page: 10.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206940Orig1s000PharmR.pdf#page=23 Page: 23.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85980	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85980
ChemicalBook	CB12723517	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12723517
MolPort	MolPort-044-183-657	https://www.molport.com/shop/molecule-link/MolPort-044-183-657
ZINC	ZINC000014210876	http://zinc15.docking.org/substances/ZINC000014210876

PubMed

Title	Date	PubMed
Eluxadoline: First Global Approval.	2015 Jul	26149369

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage in adults is 100 mg twice daily taken with food. • The recommended dosage is 75 mg twice daily taken with food in patients who: * do not have a gallbladder * are unable to tolerate the 100 mg dose * are receiving concomitant OATP1B1 inhibitors * have mild or moderate hepatic impairment • Discontinue VIBERZI in patients who develop severe constipation for more than 4 days • If a dose is missed, take the next dose at the regular time; do not take 2 doses at once

Route of Administration: Oral

In Vitro Use Guide

In the guinea pig isolated ileum, MuDelta (eluxadoline) reduced electrical field stimulation-evoked contractions similar to DAMGO, with Kis of 1.0 and 1.3 nM, respectively. ) In guinea pig isolated proximal colon, MuDelta (eluxadoline) had weak k opioid receptor agonist activity compared with the k opioid receptor agonist ICI 204 448, with IC50 = 1.6 mM and 1.7 nM, respectively

Name

Type

Language

ELUXADOLINE DIHYDROCHLORIDE

Common Name

English

BENZOIC ACID, 5-((((2S)-2-AMINO-3-(4-(AMINOCARBONYL)-2,6-DIMETHYLPHENYL)-1-OXOPROPYL)((1S)-1-(5-PHENYL-1H-IMIDAZOL-2-YL)ETHYL)AMINO)METHYL)-2-METHOXY-, HYDROCHLORIDE (1:2)

Systematic Name

English

ELUXADOLINE DIHYDROCHLORIDE [MI]

Common Name

English

MUDELTA

Brand Name

English

Code System Code Type Description

FDA UNII

7U4JQA48TT