Minirin Mechanism of Action

Pharmacotherapeutic group: vasopressin and analogues. ATC code: H01B A02.
Pharmacology: Pharmacodynamics: 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.
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: Absorption: The plasma concentration of desmopressin has been shown to be equivalent after administration of MINIRIN tablet 2x 0.2 mg (0.4 mg) and MINIRIN Oral Lyophilisate 240 mcg respectively.
The mean bioavailability of desmopressin administered sublingually as MINIRIN Oral Lyophilisate is approximately 0.25%. Concomitant intake of food has not been investigated with MINIRIN Oral Lyophilisate 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 Cmax was 14, 30 and 65 pg/mL respectively. Tmax 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% of the amount of administered desmopressin is found in the urine.
Paediatric Population: The population pharmacokinetics has been studied in children (6-12 years) with PNE and is comparable to that in adults.