Glypressin Mechanism of Action

Pharmacotherapeutic group: Posterior pituitary lobe hormones (vasopressin and analogues). ATC code: H01BA04.
Pharmacology: Pharmacodynamics: Terlipressin initially has an effect of its own, but is converted by enzymatic cleavage to lysine vasopressin. Doses of 1 and 2 mg terlipressin acetate effectively reduce the portal venous pressure and produce marked vasoconstriction. The lowering of portal pressure and azygos blood flow is dependent on dose. The effect of the low dose is reduced after 3 hours, while haemodynamic data show that 2 mg terlipressin acetate is more effective than 1 mg as the higher dose produces a dependable effect throughout the period of treatment (4 hours).
Pharmacokinetics: The pharmacokinetics follows a two-compartment model. It has been found that the half-life is approximately 40 min., metabolic clearance is approximately 9 ml/kg/min and the distribution volume is approximately 0.5 l/kg.
The desired concentration of lysine vasopressin in plasma is found initially after approximately 30 min. and reaches a peak value of 60 to 120 min. after administration of GLYPRESSIN. Because of 100% cross-reaction between terlipressin and lysine vasopressin, there is no specific RIA method for these substances.
Toxicology: Preclinical safety data: Preclinical data reveal no special hazard for humans based on conventional studies of single- and repeat-dose toxicity, and genotoxicity. At dosages relevant to humans, the only effects observed in animals were those attributable to the pharmacological activity of terlipressin.
No pharmacokinetic data are available from animals to compare with humans the plasma concentrations at which these effects occurred, but as the route of administration was intravenous, a substantial systemic exposure can be assumed for the animal studies.
An embryo-fetal study in rats demonstrated no adverse effects of terlipressin, but in rabbits abortions occurred, probably related to maternal toxicity, and there were ossification anomalies in a small number of fetuses and a single isolated case of cleft palate.
No carcinogenicity studies have been performed with terlipressin.