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
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)
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).
Originator
Approval Year
Cmax
AUC
T1/2
Doses
AEs
Sourcing
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
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).