Radioimmunoassay of desglycinamide-arginine vasopressin and its application in a pharmacokinetic study in the rat.
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.
Center for Bio-Pharmaceutical Sciences, State University of Leiden, The Netherlands.
J B
JB
van Bree
A G
AG
de Boer
M
M
Danhof
J C
JC
Verhoef
T B
TB
van Wimersma Greidanus
D D
DD
Breimer
D000818:Animals; D000906:Antibodies; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics; D003429:Cross Reactions; D005260:Female; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains
D000906:Antibodies; D001127:Arginine Vasopressin; C015119:argipressin, des-GlyNH2(9)-