Tolvaptan
Synonym(s):N-[4-[(7-Chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methylbenzamide;OPC 41061
- CAS NO.:150683-30-0
- Empirical Formula: C26H25ClN2O3
- Molecular Weight: 448.94
- MDL number: MFCD09838782
- EINECS: 691-537-5
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-04-10 13:06:19
What is Tolvaptan?
Absorption
Tmax, Healthy subjects: 2 - 4 hours; Cmax, Healthy subjects, 30 mg: 374 ng/mL; Cmax, Healthy subjects, 90 mg: 418 ng/mL; Cmax, heart failure patients, 30 mg: 460 ng/mL; Cmax, heart failure patients, 90 mg: 723 ng/mL; AUC(0-24 hours), 60 mg: 3.71 μg·h/mL; AUC(∞), 60 mg: 4.55 μg·h/mL; The pharmacokinetic properties of tolvaptan are stereospecific, with a steady-state ratio of the S-(-) to the R-(+) enantiomer of about 3. The absolute bioavailability of tolvaptan is unknown. At least 40% of the dose is absorbed as tolvaptan or metabolites. Food does not impact the bioavailability of tolvaptan.
Toxicity
The oral LD50 of tolvaptan in rats and dogs is >2000 mg/kg. Most common adverse reactions (≥5% placebo) are thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia.
Description
The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-proteincoupled receptor subtypes:V1-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135 mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2receptor promotes water excretion without perturbing electrolyte balance making it an appealing target for preventing disease progression. Following the introduction of the dual AVP V1a/V2 receptor antagonist conivaptan, tolvaptan has recently been launched as a nonpeptide, selective V2 receptor antagonist with potent aquaretic attributes for the treatment of hypervolemic and euvolemic hyponatremia (serum sodium concentration of <125 mmol/L or less distinct hyponatremia that is symptomatic and has resisted correction with fluid restriction). As a more potent and selective V2 receptor antagonist, tolvaptan is a follow-up to mozavaptan, which possesses weak V1 receptor antagonism and was approved for the treatment of SIADH in Japan. .
The Uses of Tolvaptan
Tolvaptan (OPC-41061) is a selective, competitive arginine vasopressin receptor 2 antagonist with an IC50 of 1.28μM for the inhibition of AVP-induced platelet aggregation. Tolvaptan (OPC-41061) is used to treat hyponatremia (low blood sodium levels) assoc
What are the applications of Application
Tolvaptan is a selective vasopressin receptor 2 antagonist
Indications
Treatment of symptomatic and resistant to fluid restriction euvolemic or hypervolemic hyponatremia associated with congestive heart failure, SIADH, and cirrhosis.
Background
Tolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH). FDA approved on May 19, 2009.
Pharmacokinetics
Urine volume and fluid intake increase in a dose dependent manner which results in overall negative fluid balance in patients taking tolvaptan. Increases in serum sodium and osmolality can be observed 4-8 hours post-administration and is maintained for 24 hours. The magnitude of serum sodium and osmolality change increases with escalating doses. Furthermore, a decrease in urine osmolality and increase in free water clearance can be observed 4 hours after post-administration of tolvaptan. The affinity for V2 receptors is 29x greater than that of V1a receptors and does not have any appreciable affinity for V2 receptors.
Metabolism
Metabolism exclusively by CYP3A4 enzyme in the liver. Metabolites are inactive.
Properties of Tolvaptan
Melting point: | 219-222°C |
Boiling point: | 594.4±50.0 °C(Predicted) |
Density | 1.311±0.06 g/cm3(Predicted) |
storage temp. | 2-8°C |
solubility | DMSO: ≥15mg/mL |
form | powder |
color | white to tan |
Safety information for Tolvaptan
Computed Descriptors for Tolvaptan
InChIKey | GYHCTFXIZSNGJT-UHFFFAOYSA-N |
SMILES | C(NC1=CC=C(C(N2C3=CC=C(Cl)C=C3C(O)CCC2)=O)C(C)=C1)(=O)C1=CC=CC=C1C |
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ASolution Pharmaceuticals Pvt Ltd
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