Tolvaptan Sodium Phosphate
[CAS# 942619-79-6]

Identification

• Classification: Biochemical >> Inhibitor >> G protein coupled receptor(GPCR & G Protein)
• Name: Tolvaptan Sodium Phosphate
• Synonyms: disodium [7-chloro-1-[2-methyl-4-[(2-methylbenzoyl)amino]benzoyl]-2,3,4,5-tetrahydro-1-benzazepin-5-yl] phosphate
• Molecular Formula: C₂₆H₂₄ClN₂Na₂O₆P
• Molecular Weight: 572.88
• CAS Registry Number: 942619-79-6
• SMILES: CC1=CC=CC=C1C(=O)NC2=CC(=C(C=C2)C(=O)N3CCCC(C4=C3C=CC(=C4)Cl)OP(=O)([O-])[O-])C.[Na+].[Na+]

Discovory and Applicatios

Tolvaptan sodium phosphate is an intravenously administered prodrug of tolvaptan, a selective vasopressin V₂ receptor antagonist. This compound was developed to overcome the limitations associated with the oral administration of tolvaptan, particularly in patients who cannot take medications orally due to impaired consciousness, gastrointestinal dysfunction, or mechanical ventilation. The phosphate group added to the molecular structure enhances water solubility, making it suitable for intravenous use in acute clinical settings.

The compound works by inhibiting vasopressin at V₂ receptors located in the renal collecting ducts. This action prevents the insertion of aquaporin-2 water channels into the apical membrane, reducing water reabsorption and promoting free water excretion—a process termed aquaresis. Unlike conventional diuretics, tolvaptan sodium phosphate induces water loss without significantly affecting electrolyte levels, making it particularly useful in correcting hyponatremia and managing fluid overload in conditions like heart failure.

Tolvaptan sodium phosphate was developed to meet the clinical need for an effective vasopressin antagonist that could be administered intravenously. The compound undergoes enzymatic hydrolysis in the body, releasing active tolvaptan, which then binds to V₂ receptors. This pharmacological approach ensures rapid onset of action, which is critical in managing acute decompensated heart failure and other emergency settings.

The typical dosing involves an intravenous infusion of 16 mg once daily over one hour. This regimen has shown effectiveness in increasing urine volume and decreasing urine osmolality, outcomes that are consistent with the mechanism of aquaresis. The absence of significant changes in serum sodium beyond the desired correction range further supports its safety profile in clinical use. Furthermore, it provides an option when loop diuretics or other standard therapies are inadequate or contraindicated.

Clinical investigations have shown that patients treated with tolvaptan sodium phosphate experienced meaningful improvements in fluid balance and clinical symptoms. These findings underscore its utility in managing cases where traditional therapies are not effective. The formulation allows precise control over drug delivery and dosing, which is important in critically ill patients who require rapid fluid management without the risk of excessive electrolyte loss.

Tolvaptan sodium phosphate was approved for medical use in Japan and has since been used under the name SAMTASU®. It is specifically indicated for patients with heart failure experiencing volume overload and for whom oral administration is not possible. Its approval represents a milestone in the pharmacological management of heart failure, particularly for hospitalized patients who may not be candidates for oral medications.

In medical practice, tolvaptan sodium phosphate is employed when rapid diuresis is needed without compromising serum sodium levels. It is a valuable therapeutic option that complements existing diuretics by providing a mechanism focused on water elimination rather than sodium or chloride excretion. Its introduction into treatment protocols has contributed to improved outcomes in patient populations with complex fluid management needs.

The development and application of tolvaptan sodium phosphate illustrate the importance of targeted drug delivery and formulation improvements in optimizing pharmacotherapy. The compound fulfills a specific clinical requirement and serves as an example of how chemical modification can extend the utility of existing drugs to meet new therapeutic challenges. It is a practical addition to the available treatment modalities for fluid overload in hospitalized and critically ill patients.