Summary
The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA.
Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1.
The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions.
The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andersson K-E, Arner B (1972) Effects of dDAVP, a synthetic analogue of vasopressin, in patients with central diabetes insipidus. Acta Med Scand 192: 21–27
Carver MJ, Paska R (1961) Ion-exchange chromatography of urinary aminoacids. Clin Chim Acta 6: 721–724
Fjellestad A, Czernichow P (1986) Central diabetes insipidus in children. Oral treatment with a vasopressin hormone analog (dDAVP). Acta Paediatr Scand 75: 605–610
Fjellestad-Paulsen A, Tubiana-Rufi N, Harris AS, Czernichow P (1987) Central diabetes insipidus in children. Antidiuretic effect and pharmacokinetics of intra-nasal and peroral 1-Deamino-8-D-Arginine Vasopressin. Acta Endocrinol 115: 307–312
Fjellestad-Paulsen A, Höglund P, Lundin S, Paulsen O (1993) Pharmacokinetics of 1-deamino-8-D-Arginine vasopressin after various routes of administration in healthy volunteers. Clin Endocrinol 38: 177–182
Hammer M, Vilhardt H (1985) Peroral treatment of diabetes insipidus with a polypeptide hormone analog, Desmopressin. J Pharmacol Exp Ther 234: 754–760
Van de Heyning BJM, Koekkoch van den Herik I, Ivanyi T, van Wimersma G, Reidanus TB (1991) Solid-phase extraction of plasma vasopressin = evaluation, validation and application. J Chromatogr 565: 159–171
Köhler M, Harris A (1988) Pharmacokinetics and haematological effects of vasopressin. Eur J Clin Pharmacol 35: 281–285
Lundin S, Melin P, Vilhardt H (1985) Plasma concentrations of 1-deamino-8-D-arginine vasopressin after intragastric administration in the rat. Acta Endocrinol (Copenhagen) 108: 170–183
Lundin S, Vilhardt H (1986) Absorption of 1-deamino-8-D-arginine vasopressin from different regions of the gastro-intestinal tract in rabbits. Acta Endocrinol (Copenhagen) 112: 457–460
Lundin A, Pantzar N, Broeders A, Ohlin M, Weström BR (1991) Differences in transport rate of oxytocin and vasopressin analogues across proximal and distal isolated segments of the small intestine of the rat. Pharm Res 8: 1274–1280
Modigliani R, Rambaud JC, Bernier JJ (1973) The method of intraluminal perfusion of the human small intestine. Principle and technique. Digestion 9: 176–192
Saffran M, Bedra C, Kumar GS, Neckers DC (1988) Vasopressin: a model for the study of effects of additives on the oral and rectal administration of peptide drugs. J Pharmaceutical Sci 77: 33–38
Seif SM, Zenser TV, Ciarochi FF, Davis BB, Robinson AG (1978) dDAVP (1-Desamino-8-D-arginine-vasopressin) Treatment of central diabetes insipidus-mechanism of prolonged antidiuresis. J Clin Endocrinol Metab 46: 381–388
Statistical Consultants (1986). PCNONLIN and NONLIN84 Software for the statistical analysis of nonlinear models. Am Statist 40: 52
Vilhardt H, Bie P (1983) Antidiuretic response in conscious dogs following peroral administration of arginine vasopressin and its analogues. Eur J Pharmacol 93: 201–204
Vilhardt H, Bie P (1984) Antidiuretic effect of perorally administered dDAVP in hydrated humans. Acta Endocrinol (Copenhagen) 105: 474–476
Vilhardt H, Lundin S (1986) In vitro intestinal transport of vasopressin and its analogues. Acta Physiol Scand 126: 601–607
Vilhardt H, Lundin S (1986) Biological effect and plasma concentrations of dDAVP after intranasal and peroral administration to humans. Gen Phamacol 17: 481–483
Vilhardt H, Lundin S, Falck J (1986) Plasma kinetics of dDAVP in man. Acta Pharmacol Toxicol 58: 379–381
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
d'Agay-Abensour, L., Fjellestad-Paulsen, A., Höglund, P. et al. Absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in man. Eur J Clin Pharmacol 44, 473–476 (1993). https://doi.org/10.1007/BF00315546
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315546