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[EFFECTS OF ORALLY AND PARENTERALLY ADMINISTERED ANALOGS OF PEPTIDE HORMONES ON RENAL WATER AND ION TRANSPORT].
Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova
|September 8, 2018
Summary
Oral administration of neurohypophysial hormone analogs to rats showed preserved physiological activity, but required higher doses. Inhibiting gastrointestinal proteases improved peptide absorption and efficacy.
Area of Science:
- Pharmacology
- Endocrinology
- Gastroenterology
Background:
- Neurohypophysial hormones and their analogs are crucial for regulating water and electrolyte balance.
- The gastrointestinal tract presents a barrier to peptide drug absorption due to enzymatic degradation and low permeability.
- Understanding oral bioavailability of peptide-based therapeutics is vital for drug development.
Purpose of the Study:
- To investigate the physiological activity and oral bioavailability of neurohypophysial hormone analogs administered via the gastrointestinal tract.
- To evaluate the impact of gastrointestinal protease inhibition on the efficacy of orally administered nonapeptides.
- To compare the oral activity of neurohypophysial hormone analogs with a glucagon-like peptide-1 mimetic.
Main Methods:
- Experiments were conducted using female Wistar rats.
- Neurohypophysial hormone analogs and exenatide were administered orally and intramuscularly.
- Antidiuretic and natriuretic effects were measured.
- The effect of aprotinine (a protease inhibitor) on peptide absorption and activity was assessed.
Main Results:
- Oral administration of deamino-vasotocin analogs preserved physiological activity, increasing water reabsorption and electrolyte excretion.
- Oral doses required were 50-200 times higher than intramuscular doses.
- Aprotinine enhanced nonapeptide effects, with approximately 0.5% absorption of orally introduced substance.
- Exenatide showed no physiological effects after oral administration but increased electrolyte excretion after intramuscular injection.
Conclusions:
- Neurohypophysial hormone analogs retain physiological activity upon oral administration, albeit with reduced potency.
- Gastrointestinal protease inhibition can enhance the efficacy of orally delivered nonapeptides.
- The oral route is less effective for exenatide compared to neurohypophysial hormone analogs, suggesting different absorption or degradation pathways.