Desmopressin Acetate Injection 4 mcg/mL is a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation. It is chemically defined as follows:
Mol. Wt. 1183.34
Molecular Formula: C46H64N14O12S2• C2H4O2• 3H2O
1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.
Desmopressin Acetate Injection 4 mcg/mL is provided as a sterile, aqueous solution for intravenous or subcutaneous use. Each mL contains desmopressin acetate, 4 mcg and sodium chloride, 9 mg. May contain hydrochloric acid for pH adjustment. pH is 4.0 (3.5 to 5.0).
Desmopressin Acetate Injection 4 mcg/mL contains as active substance, 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin, a synthetic analogue of the natural hormone arginine vasopressin. One mL (4 mcg) of desmopressin acetate solution has an antidiuretic activity of about 16 IU; 1 mcg of desmopressin acetate is equivalent to 4 IU.
Desmopressin acetate has been shown to be more potent than arginine vasopressin in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand’s disease Type I.
Dose-response studies were performed in healthy persons, using doses of 0.1 to 0.4 mcg/kg body weight, infused over a 10-minute period. Maximal dose response occurred at 0.3 to 0.4 mcg/kg. The response to desmopressin acetate of factor VIII activity and plasminogen activator is dose-related, with maximal plasma levels of 300 to 400 percent of initial concentrations obtained after infusion of 0.4 mcg/kg body weight. The increase is rapid and evident within 30 minutes, reaching a maximum at a point ranging from 90 minutes to two hours. The factor VIII related antigen and ristocetin cofactor activity were also increased to a smaller degree, but still are dose-dependent.
The biphasic half-lives of desmopressin acetate were 7.8 and 75.5 minutes for the fast and slow phases, respectively, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone. As a result, desmopressin acetate provides a prompt onset of antidiuretic action with a long duration after each administration.
The change in structure of arginine vasopressin to desmopressin acetate has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle.
When administered by injection, desmopressin acetate has an antidiuretic effect about ten times that of an equivalent dose administered intranasally.
The bioavailability of the subcutaneous route of administration was determined qualitatively using urine output data. The exact fraction of drug absorbed by that route of administration has not been quantitatively determined.
The percentage increase of factor VIII levels in patients with mild hemophilia A and von Willebrand’s disease was not significantly different from that observed in normal healthy individuals when treated with 0.3 mcg/kg of desmopressin acetate infused over 10 minutes.
Plasminogen activator activity increases rapidly after desmopressin acetate infusion, but there has been no clinically significant fibrinolysis in patients treated with desmopressin acetate.
The effect of repeated desmopressin acetate administration when doses were given every 12 to 24 hours has generally shown a gradual diminution of the factor VIII activity increase noted with a single dose. The initial response is reproducible in any particular patient if there are 2 or 3 days between administrations.