U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C27H21ClFN3O2
Molecular Weight 473.926
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LIXIVAPTAN

SMILES

CC1=C(C=C(F)C=C1)C(=O)NC2=CC(Cl)=C(C=C2)C(=O)N3CC4=CC=CN4CC5=C3C=CC=C5

InChI

InChIKey=PPHTXRNHTVLQED-UHFFFAOYSA-N
InChI=1S/C27H21ClFN3O2/c1-17-8-9-19(29)13-23(17)26(33)30-20-10-11-22(24(28)14-20)27(34)32-16-21-6-4-12-31(21)15-18-5-2-3-7-25(18)32/h2-14H,15-16H2,1H3,(H,30,33)

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318867.pdf http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM320601.pdf

Lixivaptan is an orally-active, vasopressin 2 receptor antagonist. It is indicated for the treatment of symptomatic hypervolemic and euvolemic hyponatremia, associated with heart failure (HF) and syndrome of inappropriate antidiuretic hormone (SIADH). Adverse events likely to be result of the pharmacologic action of lixivaptan are: constipation, dry mouth, dizziness, insomnia. Grapefruit juice significantly increased the extent of lixivaptan absorption as compared to lixivaptan administered under fasted conditions but not under fed conditions. Lixivaptan Cmax and AUC∞ increased by 2.4-fold and 3.2-fold, respectively, when lixivaptan was administered with ketoconazole (the same in case of Simvastatin).

Approval Year

TargetsConditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1877 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
719 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
183 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1208 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
210 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14884 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4391 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
499 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8775 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
953 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.62 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.05 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.61 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
22.56 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
12.49 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIXIVAPTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
300 mg single, oral
Highest studied dose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources: Page: p.1202
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: Cirrhosis
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 5
Sources: Page: p.1202
250 mg 2 times / day multiple, oral
Studied dose
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.187, 188
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cirrhosis of liver
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources: Page: p.187, 188
Disc. AE: Blood sodium increased...
AEs leading to
discontinuation/dose reduction:
Blood sodium increased (50%)
Sources: Page: p.187, 188
AEs

AEs

AESignificanceDosePopulation
Blood sodium increased 50%
Disc. AE
250 mg 2 times / day multiple, oral
Studied dose
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.187, 188
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cirrhosis of liver
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources: Page: p.187, 188
PubMed

PubMed

TitleDatePubMed
5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin antagonist with selectivity for V2 receptors.
1998 Jul 2
Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463.
2000 Oct
Patents

Sample Use Guides

The starting dose for hospitalized patients with hyponatremia is 50 mg once daily (25 mg for outpatients) without regard to meals. The dose may be doubled every 24 hours depending on individual patient response to a maximum of 100 mg once daily (total daily dose 100 mg) in syndrome of inappropriate antidiuretic hormone patients and to a maximum of 100 mg BID (total daily dose 200 mg) in heart failure patients, as needed, to achieve the desired sodium concentration.
Route of Administration: Oral
In Vitro Use Guide
Sources: Zingg, H.H., Bourque, W.C., Bichet, D.G. (2012) 'Vasopressin and Oxytocin: Molecular, Cellular, and Clinical Advances', p.440 Retrieved from https://books.google.ru/books?id=eaXfBwAAQBAJ
Scatchard analysis of binding to cloned human V2-receptors showed that the dissociation constant (Kd) of [3H]-AVP increased from 0.79 nM in the vehicle-control to 1.04 nM in the presence of 0.5 nM VPA-985, while the maximum binding (B max) remained unchanged (1.14 vs. 1.02 fmole/ug protein, respectively).
Name Type Language
LIXIVAPTAN
DASH   INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
LIXAR
Brand Name English
lixivaptan [INN]
Common Name English
LIXIVAPTAN [MI]
Common Name English
CRTX-080
Code English
VPA-985
Code English
LIXIVAPTAN [MART.]
Common Name English
3'-CHLORO-5-FLUORO-4'-(5H-PYRROLO(2,1-C)(1,4)BENZODIAZEPIN-10(11H)-YLCARBONYL)-O-TOLUANILIDE
Common Name English
WAY-VPA-985
Code English
Lixivaptan [WHO-DD]
Common Name English
CRTX080
Code English
VPA985
Code English
BENZAMIDE, N-(3-CHLORO-4-(5H-PYRROLO(2,1-C)(1,4)BENZODIAZEPIN-10(11H)-YLCARBONYL)PHENYL)-5-FLUORO-2-METHYL-
Systematic Name English
LIXIVAPTAN [USAN]
Common Name English
LIXIVAPTAN [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2180
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
FDA ORPHAN DRUG 589617
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL49429
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
USAN
KK-109
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
DRUG BANK
DB06666
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
INN
8006
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
SMS_ID
100000126015
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
PUBCHEM
172997
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
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NCI_THESAURUS
C74429
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
CAS
168079-32-1
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
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EPA CompTox
DTXSID00168472
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
WIKIPEDIA
LIXIVAPTAN
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
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EVMPD
SUB32850
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
MERCK INDEX
m6876
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY Merck Index
FDA UNII
8F5X4B082E
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY
MESH
C409452
Created by admin on Sat Dec 16 05:04:48 GMT 2023 , Edited by admin on Sat Dec 16 05:04:48 GMT 2023
PRIMARY