Radioimmunoassay for hexarelin, a peptidic growth hormone secretagogue, and its pharmacokinetic studies.
A radioimmunoassay (RIA) method for hexarelin, a peptidic growth hormone secretagogue, has been developed and applied to pharmacokinetic studies in dogs following an IV dose of 1 microgram/kg, and three SC doses of 1, 10, and 100 micrograms/kg. The sensitivity of the assay was determined to be 1.34 fmol/assay. Cross-reactivity of the antiserum with nine hexarelin analogues was less than 1% upon modification of positions 3, 4, or 5 of the peptide. No apparent cross-reaction with endogenous hexarelin metabolites were observed. Intra- and interassay coefficients of variation were less than 3% and 4%, respectively. Intravenous bolus pharmacokinetics of hexarelin displayed a high terminal half-life of 120 min, a fractional plasma clearance of 4.28 ml/min/kg, and a volume of distribution at steady state of 387.7 ml/kg. Following SC administration of hexarelin, despite the increase in dose administered, both clearance (3.93-5.17 ml/min/kg) and volume of distribution (316-544 ml/kg) parameters remained constant over the dose range studied.
University of Montreal, Faculty of Pharmacy, Quebec, Canada.
M
M
Roumi
V
V
Lenaerts
F
F
Boutignon
P
P
Wuthrich
R
R
Deghenghi
M
M
Bellemare
A
A
Adam
H
H
Ong
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006133:Growth Substances / Q000032:analysis / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000032:analysis / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D011863:Radioimmunoassay / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; D013006:Growth Hormone