Radioimmunoassay of desglycinamide-arginine vasopressin and its application in a pharmacokinetic study in the rat

Publication Type:

Journal Article

Authors:

van Bree, J.B.; de Boer, A.G.; Danhof, M.; Verhoef, J.C.; van Wimersma Greidanus, T.B.; Breimer, D.D.

Source:

Peptides, Volume 9, Number 3, p.555-9 (1988)

ISBN:

0196-9781 (Print)

DOI Name (links to online publication)

Keywords:

Animals; Antibodies; Arginine Vasopressin/*analogs; &; derivatives/blood/immunology/pharmacokinetics; Cross Reactions; Female; Radioimmunoassay/methods; Rats; Rats; Inbred Strains

Abstract:

The purpose of this investigation was to develop a sensitive and selective radioimmunoassay for Desglycinamide-Arginine Vasopressin (DGAVP). DGAVP was extracted from rat plasma after protein precipitation, using Sep-Pak C18 cartridges and 50 mM glycine buffer/methanol (10:90) solution. Extraction recovery was 73 +/- 14% (mean +/- S.D.; n = 11) and good linearity was achieved in the concentration range of 0.25-128 pg/tube. Instantaneous tracer addition resulted in a detection limit of 250 fg/tube, whereas 24 hours preincubation and delayed tracer addition resulted in a detection limit of 100 fg/tube. Intra-assay variation ranged between 7.4% and 10.0% depending on the peptide concentration and inter-assay variation was 13.2%. Using this procedure, plasma pharmacokinetics of DGAVP in the rat were determined after IV administration. DGAVP plasma concentration showed a rapid distribution phase (t1/2 = 1.0 +/- 0.2 min) and a somewhat slower elimination phase (t1/2 = 7.2 +/- 2.1 min). High clearance values (CLss = 97 +/- 30 ml.min-1) suggest rapid metabolism by amino- and carboxy-peptidases.