Minirin Mechanism of Action

Pharmacotherapeutic group: vasopressin and analogues. ATC code: H01B A02.
Solution for injection: Properties: MINIRIN contains desmopressin, a structural analogue of the natural hormone arginine vasopressin. Two chemical changes have been made to the natural hormone, namely desamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. These structural changes result in a compound with significantly increased antidiuretic potency, very little activity on smooth muscle, hence the avoidance of undesirable pressor side effects. The duration of the antidiuretic effect is about 8-12 hours.
MINIRIN in a high dosage, 0.3 µg/kg body weight intravenously or subcutaneously, leads to a two-to-four-fold increase in plasma of factor VIII coagulant activity (VIII:C). Also the content of von Willebrand factor-antigen (vWF:Ag) increases, but to a lesser extent. At the same time there is a release of the plasminogen activator (t-PA).
Maximum plasma concentration following a dose of 0.3 µg/kg body weight, is reached after approximately 60 minutes and amounts to an average of 600 pg/ml. Plasma half life ranges between 3 and 4 hours. The duration of the haemostatic effect depends on the plasma half life for VIII:C which is about 8-12 hours.
Administration of desmopressin has also been shown to lead to a shortening or normalization of the bleeding time in patients with prolonged bleeding time as in uraemia, liver cirrhosis, congenital or drug-induced thrombocyte dysfunction and in patients with prolonged bleeding time of unknown aetiology.
The risk of transmission of HIV-infection and hepatitis virus as seen for factor VIII concentrates is avoided by administration of desmopressin.
pH of the solution is about 4.
Pharmacology: Pharmacodynamics: Tablet/Melt oral lyophilisate: MINIRIN contains desmopressin, a structural analogue of the natural pituitary hormone arginine vasopressin. The difference lies in that the amino group in cysteine has been removed and L-arginine has been substituted by D-arginine. This results in a considerably longer duration of action and a complete lack of pressor effect in the dosages used clinically. After oral administration of desmopressin (tablet), the antidiuretic effect could be expected to last 6-14 hours or more.
Clinical trials with desmopressin tablets in the treatment of nocturia showed the following: A reduction of at least 50% in the mean number of nocturnal voids was obtained in 39% of patients with desmopressin compared to 5% of patients with placebo (p<0.0001).
The mean number of voids per night decreased by 44% with desmopressin compared to 15% with placebo (p<0.0001).
The median duration of first undisturbed sleep period increased by 64% with desmopressin compared to 20% with placebo (p<0.0001).
The mean duration of first undisturbed sleep period increased by 2 hours with desmopressin compared to 31 minutes with placebo (p<0.0001).
Pharmacokinetics: Tablet: Absorption: The absolute bioavailability after perorally administered desmopressin is 0.16% (SD=0.17%). Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. Concomitant food intake decreases the rate and extent of absorption by about 40%.
The maximum plasma concentration is reached after 1-1.5 hours. C_max and AUC do not increase in proportion to the administered dose.
Distribution: The distribution volume is 0.2-0.3 l/kg. Desmopressin does not cross the blood-brain barrier.
Metabolism: In vitro studies with human liver microsomes have shown that no significant amount of desmopressin is metabolized in the liver. It is therefore unlikely that desmopressin is metabolized in the liver in human beings.
Elimination: The mean half-life for desmopressin in the elimination phase is 2-3 hours.
52% (44%-60%) of the amount of administered desmopressin is found in the urine.
Paediatric Population: The population pharmacokinetics has been studied in children with PNE and is comparable to that in adults.
Melt oral lyophilisate: Absorption: The plasma concentration of desmopressin has been shown to be equivalent after administration of MINIRIN tablets 2x0.2 mg (0.4 mg) and MINIRIN Melt 240 mcg respectively.
The mean bioavailability of desmopressin administered sublingually as MINIRIN Melt is approximately 0.25%. Concomitant intake of food has not been investigated with MINIRIN Melt but concomitant food intake with MINIRIN tablets decreases the rate and extent of absorption by 40%. Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. The plasma concentration of desmopressin increases proportionally to administered doses and after administration of 200, 400 and 800 mcg C_max was 14, 30 and 65 pg/mL respectively. T_max was reached after 0.5 - 2 hours. The terminal half-life is estimated to 2.8 hours.
Distribution: The distribution volume of desmopressin after intravenous administration is 33 L (0.41 L/kg). Desmopressin does not cross the blood-brain barrier.
Metabolism: In vitro studies with human liver microsomes have shown that no significant amount of desmopressin is metabolized in the liver. It is therefore unlikely that desmopressin is metabolized in the liver in human beings.
Elimination: 52% (44% - 60%) of the amount of administered desmopressin is found in the urine.
Paediatric Population: The population pharmacokinetics has been studied in children with PNE and is comparable to that in adults.