DDAVP's Active Ingredient and Composition
DDAVP (desmopressin) contains desmopressin acetate as its active ingredient, which is a synthetic analogue of the natural hormone arginine vasopressin. 1
Chemical Composition and Structure
- Desmopressin acetate has the molecular formula C46H64N14O12S2•C2H4O2•3H2O with a molecular weight of 1183.34 1
- It is chemically defined as 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate 1
- The structural modification from natural vasopressin gives desmopressin enhanced antidiuretic properties while reducing vasopressor effects 1
Formulation Components
- The nasal spray solution (0.01%) contains:
- Desmopressin acetate, USP (0.1 mg/mL)
- Sodium chloride (9 mg/mL)
- Chlorobutanol (0.5%, 5.25 mg/mL) as a preservative
- Hydrochloric acid (to adjust pH to 4.5-6)
- Water for injection 1
Pharmacological Properties
- Desmopressin has approximately 400 IU of antidiuretic activity per 1 mL (0.1 mg) 1
- 10 mcg of desmopressin acetate is equivalent to 40 IU of antidiuretic activity 1
- It has biphasic half-lives of 7.8 and 75.5 minutes for the fast and slow phases, providing prompt onset with long duration of action 1
- The intranasal route delivers about one-tenth the antidiuretic effect of an equivalent injected dose 1
- Desmopressin is primarily excreted in the urine, with terminal half-life increasing significantly in patients with renal impairment 1
Mechanism of Action
- Desmopressin increases the concentration of von Willebrand factor and factor VIII in the bloodstream 2, 3
- It has direct effects on platelets that are not fully characterized 2
- The structural modifications from arginine vasopressin result in decreased vasopressor action and decreased effects on visceral smooth muscle while enhancing antidiuretic activity 1
- It acts through activation of endothelial vasopressin V2 receptors and cAMP-mediated signaling 4
- This leads to exocytosis from Weibel-Palade bodies where von Willebrand factor and tissue plasminogen activator are stored 4
Clinical Applications
- Used for central diabetes insipidus 5
- Effective in treating mild type I von Willebrand disease and mild hemophilia A 2, 6
- Used to manage bleeding in patients with uremia, liver cirrhosis, and platelet dysfunctions 3
- Can reduce blood loss and transfusion requirements during certain surgical procedures 3
DDAVP's unique chemical structure and pharmacological properties make it valuable as a nontransfusional hemostatic agent for various bleeding disorders, with its synthetic nature providing advantages over natural vasopressin in terms of antidiuretic potency and duration of action.