title: Pharmacokinetics of glycine-proline-glutamate, the N-terminal tripeptide of insulin-like growth factor-1, in rats.
abstract: Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-1 and has been shown to be neuroprotective following ischemia-induced brain injury. The pharmacokinetics of GPE were studied in adult rats since GPE is a candidate for use in neuroprotection therapies. To measure plasma concentrations of GPE a novel radioimmunoassay was developed whereby GPE was initially derivatized with Bolton and Hunter reagent before use in a standard homologous assay against the Bolton and Hunter iodinated form. The derivatized GPE radioimmunoassay showed a 83% recovery of unlabeled GPE and complete parallel displacement with rat plasma. The simplicity and speed of the assay described here indicate an exciting new use for a previously described technology. The pharmacokinetic studies were conducted in adult rats using a single bolus intravenous injection of GPE at 30 or 100 mg/kg and showed that GPE was rapidly cleared from the circulation. In addition, evidence of the route of the metabolic degradation of GPE is presented. The findings presented here are the first description of the pharmacokinetics of GPE and suggest that, because of its very short half-life in plasma, continuous intravenous infusion of GPE may be the preferred route of administration for use in future neuroprotection therapies.
authors.affiliation: NeuronZ Ltd, PO Box 9923, Newmarket, Auckland 1031, New Zealand. david.batchelor@neuronz.com
authors.forename: D C
authors.initials: DC
authors.lastname: Batchelor
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: J-Y
authors.initials: JY
authors.lastname: Wen
authors.forename: C
authors.initials: C
authors.lastname: Keven
authors.forename: P L
authors.initials: PL
authors.lastname: Van Zijl
authors.forename: B H
authors.initials: BH
authors.lastname: Breier
authors.forename: P D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: G B
authors.initials: GB
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I; C062053:glycyl-prolyl-glutamic acid