ODEVIXIBAT SESQUIHYDRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C37H48N4O8S2.3H2O
Molecular Weight	1535.904
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.CCCCC1(CCCC)CN(C2=CC=CC=C2)C3=C(C=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C4=CC=C(O)C=C4)C(SC)=C3)S(=O)(=O)N1.CCCCC5(CCCC)CN(C6=CC=CC=C6)C7=C(C=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C8=CC=C(O)C=C8)C(SC)=C7)S(=O)(=O)N5

InChI

InChIKey=UIYFGCAQGONAMU-ZHQCGWDOSA-N

InChI=1S/2C37H48N4O8S2.3H2O/c2*1-5-8-19-37(20-9-6-2)24-41(26-13-11-10-12-14-26)29-21-31(50-4)30(22-32(29)51(47,48)40-37)49-23-33(43)39-34(25-15-17-27(42)18-16-25)35(44)38-28(7-3)36(45)46;;;/h2*10-18,21-22,28,34,40,42H,5-9,19-20,23-24H2,1-4H3,(H,38,44)(H,39,43)(H,45,46);3*1H2/t2*28-,34+;;;/m00.../s1

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C37H48N4O8S2
Molecular Weight	740.929
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://pubmed.ncbi.nlm.nih.gov/34499340|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215498s000lbl.pdfhttp://www.io.nihr.ac.uk/wp-content/uploads/migrated_new/13610-A4250.pdf | https://www.albireopharma.com/programs/odevixibat

A-4250 (odevixibat) is a selective inhibitor of the ileal bile acid transporter (IBAT) that acts locally in the gut. Ileum absorbs glyco-and taurine-conjugated forms of the bile salts. IBAT is the first step in absorption at the brush-border membrane. A-4250 works by decreasing the re-absorption of bile acids from the small intestine to the liver, whichreduces the toxic levels of bile acids during the progression of the disease. It exhibits therapeutic intervention by checking the transport of bile acids. Studies show that A-4250 has the potential to decrease the damage in the liver cells and the development of fibrosis/cirrhosis of the liver known to occur in progressive familial intrahepatic cholestasis. A-4250 is a designated orphan drug in the USA for October 2012. A-4250 is a designated orphan drug in the EU for October 2016. A-4250 was awarded PRIME status for PFIC by EMA in October 2016. A-4250 is in phase II clinical trials by Albireo for the treatment of primary biliary cirrhosis (PBC) and cholestatic pruritus. In an open label Phase 2 study in children with cholestatic liver disease and pruritus, odevixibat showed reductions in serum bile acids and pruritus in most patients and exhibited a favorable overall tolerability profile.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ileal bile acid transporter 5 Target ID: CHEMBL2778 Sources: https://www.ema.europa.eu/en/documents/assessment-report/bylvay-epar-public-assessment-report_en.pdf\|https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	Inhibitor 8504		0.13 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pruritus due to progressive familial intrahepatic cholestasis 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215498s000lbl.pdf	Primary		Approved 8583	Bylvay Approved Use Indicated for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis Launch Date 2021

C_max

Value	Dose	Co-administered	Analyte	Population
0.47 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=39	7.2 mg single, oral dose: 7.2 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.61 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=39	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.53 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=39	7.2 mg 1 times / day multiple, oral dose: 7.2 mg route of administration: Oral experiment type: MULTIPLE co-administered: MIDAZOLAM	MIDAZOLAM	ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.167 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=176	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.289 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=176	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.07 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=176	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.6112 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.1734 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
0.3521 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.174 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	10 μg/kg single, oral dose: 10 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
0.079 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	30 μg/kg single, oral dose: 30 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
0.205 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	60 μg/kg single, oral dose: 60 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
0.385 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	100 μg/kg single, oral dose: 100 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
0.363 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	200 μg/kg single, oral dose: 200 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2.19 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=39	7.2 mg single, oral dose: 7.2 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2.94 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=39	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2.66 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=39	7.2 mg 1 times / day multiple, oral dose: 7.2 mg route of administration: Oral experiment type: MULTIPLE co-administered: MIDAZOLAM	MIDAZOLAM	ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.612 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=176	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.417 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=176	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.228 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=176	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.158 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.605 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
2.002 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.311 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	10 μg/kg single, oral dose: 10 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
0.434 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	30 μg/kg single, oral dose: 30 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
0.684 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	60 μg/kg single, oral dose: 60 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
1.809 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	100 μg/kg single, oral dose: 100 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED
2.352 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=188 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=189	200 μg/kg single, oral dose: 200 μg/kg route of administration: Oral experiment type: SINGLE co-administered:		ODEVIXIBAT plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
2.36 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=41	single, oral	ODEVIXIBAT plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
2.258 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:	ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.439 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:	ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
2.083 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=183	9.6 mg single, oral dose: 9.6 mg route of administration: Oral experiment type: SINGLE co-administered:	ODEVIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.3% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=41 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf#page=170			ODEVIXIBAT plasma	Homo sapiens

Doses

Dose	Population	Adverse events
7.2 mg 1 times / day steady, oral Highest studied dose Dose: 7.2 mg, 1 times / day Route: oral Route: steady Dose: 7.2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	Disc. AE: Acute pancreatitis... AEs leading to discontinuation/dose reduction: Acute pancreatitis (severe, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf
6 mg 1 times / day steady, oral MTD Dose: 6 mg, 1 times / day Route: oral Route: steady Dose: 6 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	unhealthy Health Status: unhealthy Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf
0.12 mg/kg 1 times / day steady, oral Studied dose Dose: 0.12 mg/kg, 1 times / day Route: oral Route: steady Dose: 0.12 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	unhealthy Health Status: unhealthy Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	Disc. AE: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (mild, 1 patient) Diarrhea (3 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf

AEs

AE	Significance	Dose	Population
Acute pancreatitis	severe, 1 patient Disc. AE	7.2 mg 1 times / day steady, oral Highest studied dose Dose: 7.2 mg, 1 times / day Route: oral Route: steady Dose: 7.2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf
Diarrhea	3 patients Disc. AE	0.12 mg/kg 1 times / day steady, oral Studied dose Dose: 0.12 mg/kg, 1 times / day Route: oral Route: steady Dose: 0.12 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	unhealthy Health Status: unhealthy Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf
Diarrhea	mild, 1 patient Disc. AE	0.12 mg/kg 1 times / day steady, oral Studied dose Dose: 0.12 mg/kg, 1 times / day Route: oral Route: steady Dose: 0.12 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf	unhealthy Health Status: unhealthy Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 OCT1 620 OATP1B1 1079 CYP2C19 2057 OATP1B3 961 CYP2C8 1057 CYP2B6 926 P-gp 1741 OAT1 725 BCRP 910 OAT3 747 MATE2-K 77 MATE1 415	BCRP 697 P-gp 2052	OATP1B3 8 BCRP 101 CYP1A2 832 MATE2-K 2 OCT2 5 P-gp 301 OAT1 28 OATP1B1 29 CYP2B6 669 MATE1 5 OAT3 4

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	no [IC50 >1 uM]
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	no [IC50 >1 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171	no [IC50 >100 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	no [IC50 >30 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	no [IC50 >30 uM]
BCRP 985	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 170	no
MATE1 416	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
MATE2-K 77	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
OAT1 730	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
OAT3 749	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
OATP1B1 1095	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
OATP1B3 970	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
OCT2 782	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
P-gp 1932	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171	no	no (co-administration study) Comment: Decreased AUC of midazolam and 1-OH midazolam by 33% and 13% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171	yes [IC50 0.0056 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 170	yes [IC50 0.013 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	yes [IC50 0.308 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	yes [IC50 0.504 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	yes [IC50 0.697 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	yes [IC50 1 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 171.0	yes [IC50 1 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 170	yes [IC50 1.2 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 170	yes [IC50 16 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 122 \| 170 \| 184	yes [IC50 16.2 uM]	no (co-administration study) Comment: Decreased AUC of midazolam and 1-OH midazolam by 33% and 13% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 122 \| 170 \| 184

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 171	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 122 \| 171 \| 185	yes		yes (co-administration study) Comment: Itraconazole increased Cmax and AUC by 52% and 66% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 41 \| 122 \| 171 \| 185

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215498Orig1s000IntegratedR.pdf Page: 130.0

PubMed

Title	Date	PubMed
The ileal bile acid transporter inhibitor A4250 decreases serum bile acids by interrupting the enterohepatic circulation.	2016 Jan	26527417
Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis.	2018 Apr 27	29704003
Effects of odevixibat on pruritus and bile acids in children with cholestatic liver disease: Phase 2 study.	2021 Sep	34182185
Odevixibat: an investigational inhibitor of the ileal bile acid transporter (IBAT) for the treatment of biliary atresia.	2022 Nov	36440482
Odevixibat: a promising new treatment for progressive familial intrahepatic cholestasis.	2022 Nov	36278881
Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial.	2022 Sep	35780807

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of BYLVAY is 40 mcg/kg once daily in the morning with a meal. If there is no improvement in pruritus after 3 months, the dosage may be increased in 40 mcg/kg increments up to 120 mcg/kg once daily not to exceed a total daily dose of 6 mg.

Route of Administration: Oral

In Vitro Use Guide

Odevixibat was found to be highly specific for the ileal (apical) bile acid transporters with IC50 = 0.13, 0.12, and 1.4 nM for the human, mouse, and canine transporters, respectively, whereas the corresponding value for the human liver (basolateral) sodium/bile acid co-transporter was found to be 93 nM. 3.125, 12.5, and 50 μM odevixibat resulted in 21%, 73%, and 84% inhibition of the sodium-stimulated uptake of 0.5 mM 14C-α-aminoisobutyric acid (AIB), respectively. The apparent Km-value for sodium-stimulated AIB-uptake in the HEK293 cells is approximately 280 uM.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 13:21:18 GMT 2025` Edited by `admin` on `Wed Apr 02 13:21:18 GMT 2025`
Record UNII	Q76KP2H4XW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BYLVAY

Preferred Name

English

ODEVIXIBAT SESQUIHYDRATE

Common Name

English

Odevixibat sesquihydrate [WHO-DD]

Common Name

English

BUTANOIC ACID, 2-(((2R)-2-((2-((3,3-DIBUTYL-2,3,4,5-TETRAHYDRO-7-(METHYLTHIO)-1,1-DIOXIDO-5-PHENYL-1,2,5-BENZOTHIADIAZEPIN-8-YL)OXY)ACETYL)AMINO)-2-(4-HYDROXYPHENYL)ACETYL)AMINO)-, HYDRATE (2:3), (2S)-

Systematic Name

English

Code System Code Type Description

SMS_ID

300000024551