ELIGLUSTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H36N2O4
Molecular Weight	404.5429
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCCC(=O)N[C@H](CN1CCCC1)[C@H](O)C2=CC=C3OCCOC3=C2

InChI

InChIKey=FJZZPCZKBUKGGU-AUSIDOKSSA-N

InChI=1S/C23H36N2O4/c1-2-3-4-5-6-9-22(26)24-19(17-25-12-7-8-13-25)23(27)18-10-11-20-21(16-18)29-15-14-28-20/h10-11,16,19,23,27H,2-9,12-15,17H2,1H3,(H,24,26)/t19-,23-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=PMC3715929

Eliglustat, marketed by Genzyme as CERDELGA, is a glucosylceramide synthase inhibitor indicated for the long-term treatment of type 1 Gaucher disease who are CYP2D6 extensive metabolizers, intermediate metabolizers, or poor metabolizers (PMs) as detected by an FDA-cleared test.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ceramide glucosyltransferase 9 Target ID: Q16739 Gene ID: 7357.0 Gene Symbol: UGCG Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=25239269	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gaucher's disease type I 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf	Secondary		Approved 8429	CERDELGA Approved Use Indicated for the long-term treatment of adult patients with Gaucher disease type 1 Launch Date 2014

C_max

Value	Dose	Analyte	Population
158 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
265 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	350 mg 2 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
303 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	350 mg 2 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
4.83 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
130 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1852 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	30 mg/kg single, oral dose: 30 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
267 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	0.3 mg/kg single, oral dose: 0.3 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
88.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
91.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
79.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
12.1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf	84 mg 2 times / day multiple, oral dose: 84 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ELIGLUSTAT TARTRATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1042 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	350 mg 2 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1776 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	350 mg 2 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
21.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
556 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
62.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
10528 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	30 mg/kg single, oral dose: 30 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
112 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
151 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1562 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	0.3 mg/kg single, oral dose: 0.3 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
623 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
692 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
696 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
76.3 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf	84 mg 2 times / day multiple, oral dose: 84 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ELIGLUSTAT TARTRATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
5.77 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.64 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	350 mg 2 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	350 mg 2 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
4.32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	30 mg/kg single, oral dose: 30 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	2 mg/kg single, oral dose: 2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	0.3 mg/kg single, oral dose: 0.3 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20864621	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ELIGLUSTAT TARTRATE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf	84 mg 2 times / day multiple, oral dose: 84 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ELIGLUSTAT TARTRATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
17% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf	84 mg 2 times / day multiple, oral dose: 84 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELIGLUSTAT TARTRATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg/kg 1 times / day single, oral Highest studied dose Dose: 30 mg/kg, 1 times / day Route: oral Route: single Dose: 30 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	healthy, mean age 26 years n = 74 Health Status: healthy Age Group: mean age 26 years Sex: M Population Size: 74 Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	DLT: Bradycardia, Dizziness... Other AEs: Dizziness, Nausea... Dose limiting toxicities: Bradycardia (grade 2, 1.3%) Dizziness (grade 3, 1.3%) Dysequilibrium (grade 2, 1.3%) Hypotension (grade 2, 1.3%) Vomiting (grade 2, 1.3%) Other AEs: Dizziness (grade 2, 1.3%) Nausea (grade 2, 1.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/
20 mg/kg 1 times / day single, oral MTD Dose: 20 mg/kg, 1 times / day Route: oral Route: single Dose: 20 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	healthy, mean age 26 years n = 74 Health Status: healthy Age Group: mean age 26 years Sex: M Population Size: 74 Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	Other AEs: Nausea... Other AEs: Nausea Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/
200 mg 2 times / day multiple, oral MTD Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	healthy, mean age 28 years n = 24 Health Status: healthy Age Group: mean age 28 years Sex: M+F Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	Other AEs: Nausea... Other AEs: Nausea (grade 1-2, 12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/
350 mg 2 times / day multiple, oral Studied dose Dose: 350 mg, 2 times / day Route: oral Route: multiple Dose: 350 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	healthy, mean age 28 years n = 24 Health Status: healthy Age Group: mean age 28 years Sex: M+F Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/	Other AEs: Vomiting, Nausea... Other AEs: Vomiting (16.7%) Nausea (grade 1-2, 29.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/20864621/
100 mg 2 times / day multiple, oral (mean) Studied dose 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/2014/205494Orig1s000MedR.pdf Page: nda/2014/205494Orig1s000MedR.pdf - p.135	unhealthy, mean age 37.1 years n = 393 Health Status: unhealthy Condition: Gaucher disease type 1 Age Group: mean age 37.1 years Sex: M+F Population Size: 393 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000MedR.pdf Page: nda/2014/205494Orig1s000MedR.pdf - p.135	Other AEs: Atrioventricular block second degree, Atrioventricular block... Other AEs: Atrioventricular block second degree (1%) Atrioventricular block (<1%) Atrioventricular block first degree (<1%) Sinoatrial block (<1%) Supraventricular tachycardia (1%) Arrhythmia supraventricular (<1%) Atrial tachycardia (<1%) Ventricular tachycardia (1%) Ventricular extrasystoles (<1%) Tachycardia (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000MedR.pdf Page: nda/2014/205494Orig1s000MedR.pdf - p.135
100 mg 2 times / day multiple, oral (mean) Studied dose 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/2014/205494Orig1s000MedR.pdf Page: nda/2014/205494Orig1s000MedR.pdf - p.140	unhealthy, mean age 37.1 years n = 393 Health Status: unhealthy Condition: Gaucher disease type 1 Age Group: mean age 37.1 years Sex: M+F Population Size: 393 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000MedR.pdf Page: nda/2014/205494Orig1s000MedR.pdf - p.140	Other AEs: Nasopharyngitis, Upper respiratory tract infection... Other AEs: Nasopharyngitis (13%) Upper respiratory tract infection (11%) Influenza (6%) Sinusitis (6%) Infection urinary tract (6%) Bronchitis (3%) Gastroenteritis (3%) Viral infection (3%) Gastroenteritis viral (2%) Ear infection (2%) Oral herpes (2%) Pharyngitis (2%) Pneumonia (2%) Diarrhoea (10%) Abdominal pain upper (8%) Nausea (8%) Dyspepsia (7%) Abdominal pain (6%) Constipation (6%) Gastrooesophageal reflux disease (5%) Vomiting (4%) Abdominal distension (3%) Dysphagia (2%) Flatulence (2%) Toothache (2%) Gastritis (2%) Dry mouth (2%) Headache (17%) Dizziness (10%) Paraesthesia (2%) Neuropathy peripheral (2%) Syncope (2%) Dysgeusia (2%) Somnolence (2%) Arthralgia (14%) Back pain (9%) Pain in extremity (8%) Bone pain (5%) Myalgia (3%) Musculoskeletal pain (3%) Fatigue (7%) Asthenia (4%) Oedema peripheral (4%) Chest pain (3%) Pyrexia (3%) Influenza like illness (2%) Cough (6%) Epistaxis (4%) Oropharyngeal pain (4%) Nasal congestion (2%) Throat irritation (2%) Blood creatine phosphokinase increased (5%) Weight decreased (2%) ALT increased (2%) Rash (2%) Pruritus (2%) Dermatitis contact (2%) Dry skin (2%) Laceration (2%) Contusion (2%) Palpitations (5%) Dysmenorrhoea (2%) Metrorrhagia (2%) Splenomegaly (2%) Anxiety (2%) Hypertension (2%) Flushing (2%) Haematuria (2%) Hepatomegaly (2%) Hypersensitivity (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000MedR.pdf Page: nda/2014/205494Orig1s000MedR.pdf - p.140

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP2J2 16 BCRP 699 OATP1B1 788 MRP 7 OAT1 599	P-gp 1537 BCRP 561 OATP1B1 406 OAT1 326	CYP1A2 701 CYP2B6 547 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP2J2 19	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=110 Page: 110.0	no
MRP 7	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=112 Page: 112.0	yes [IC50 22 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=108 Page: 108.0	yes [Ki 27 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=108 Page: 108.0	yes [Ki 5.82 uM]	yes (co-administration study) Comment: Following multiple doses of eliglustat 150 mg BID, systemic exposures (AUC and Cmax) to metoprolol increased compared to metoprolol administration alone. In EMs, AUC and Cmax increased by 132% and 72% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=108 Page: 108.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205494s003lbl.pdf#page=11 Page: 11.0	major	yes (co-administration study) Comment: Following multiple doses of CERDELGA 127 mg twice daily (1.5 times the recommended dosage), metoprolol (a CYP2D6 substrate) mean Cmax and AUC increased by 1.7-fold and 2.3- fold in CYP2D6 EMs, respectively, and by 1.2-fold and 1.6-fold in IMs, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205494s003lbl.pdf#page=11 Page: 11.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205494s003lbl.pdf#page=11 Page: 11.0	minor	yes (co-administration study) Comment: As enzyme substrate: In healthy subjects, co-administration with a strong CYP2D6 and a weak CYP3A inhibitor paroxetine and a strong CYP3A inhibitor ketoconazole increased steady state eliglustat AUC Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205494s003lbl.pdf#page=11 Page: 11.0
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=112 Page: 112.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205494Orig1s000ClinPharmR.pdf#page=167 Page: 167.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:82752	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82752
ChemicalBook	CB52627796	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52627796
MolPort	MolPort-035-683-370	https://www.molport.com/shop/molecule-link/MolPort-035-683-370
ZINC	ZINC000072267023	http://zinc15.docking.org/substances/ZINC000072267023

PubMed

Title	Date	PubMed
Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study.	2010 Nov 18	20713962
Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain.	2012 Feb	22058426
Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment.	2014 Dec	24835462

Patents

Sample Use Guides

In Vivo Use Guide

CYP2D6 extensive metabolizers (Ems) or intermediate metabolizers (IMs): 84 mg orally twice daily (2.2); CYP2D6 poor metabolizers (PMs): 84 mg orally once daily (2.2); Swallow capsules whole, do not crush, dissolve or open capsules (2.3); Avoid eating grapefruit or drinking grapefruit juice

Route of Administration: Oral

In Vitro Use Guide

Studies of eliglustat potency and efficacy in cell systems showed the reduction in GL-1 in a human microsome assay and in human K562 erythropoietic cells with an IC50 of around 20 nM. In murine and canine cells, potency was a lower with IC50 values of around 60 nM and 80 nM respectively.

Name

Type

Language

ELIGLUSTAT

Official Name

English

GENZ 99067

Code

English

N-((1R,2R)-2-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-2-HYDROXY-1-(PYRROLIDIN-1- YLMETHYL)ETHYL)OCTANAMIDE

Systematic Name

English

GENZ-99067

Code

English

ELIGLUSTAT [VANDF]

Common Name

English

OCTANAMIDE, N-((1R,2R)-2-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-2-HYDROXY-1-(1- PYRROLIDINYLMETHYL)ETHYL)-

Systematic Name

English

Eliglustat [WHO-DD]

Common Name

English

ELIGLUSTAT [USAN]

Common Name

English

ELIGLUSTAT [MI]

Common Name

English

eliglustat [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

A16AX10