Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides.

Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.

An investigation of reconstituted terlipressin infusion stability for use in hepatorenal syndrome.

Hepatorenal syndrome (HRS) is a fatal complication of renal dysfunction associated with ascites, liver failure and advanced cirrhosis. Although the best option for long-term survival is liver transplantation, in the critical acute phase, vasoconstrictors are considered first-line supportive agents. Terlipressin is the most widely used vasoconstrictor globally but owing to its short elimination half-life, it is usually administered six hourly by slow intravenous bolus injection. This requires patients to remain in hospital, increasing hospital bed costs and affecting their quality of life. An alternative option for administration of terlipressin is as a continuous infusion using an elastomeric infusor device in the patient's home. However, stability data on terlipressin in elastomeric infusor devices is lacking. This research aimed to evaluate the stability of terlipressin reconstituted in infusor devices for up to 7 days at 2-8 °C and subsequently at 22.5 °C for 24 h, to mimic home storage and administration temperatures. We report that terlipressin was physically and chemically stable under these conditions; all reconstituted infusor concentrations retained above 90% of the original concentration over the test conditions. No colour change or precipitation in the solutions were evident.