Pharmacokinetics of glycine–proline–glutamate, the N-terminal tripeptide of insulin-like growth factor-1, in rats

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 meas...

Full description

Saved in:
Bibliographic Details
Published in:Analytical biochemistry 2003-12, Vol.323 (2), p.156-163
Main Authors: Batchelor, D.C, Lin, H, Wen, J.-Y, Keven, C, Zijl, P.L.Van, Breier, B.H, Gluckman, P.D, Thomas, G.B
Format: Article
Language:English
Subjects:
Animals
Bolton and Hunter reagent
Chromatography, High Pressure Liquid
Derivatization
GPE
HPLC
Insulin-Like Growth Factor I - chemistry
Insulin-Like Growth Factor I - pharmacokinetics
Male
Oligopeptides - pharmacokinetics
Peptide Fragments - chemistry
Peptide Fragments - pharmacokinetics
Radioimmunoassay
Rats
Rats, Wistar
Sensitivity and Specificity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0003-2697
1096-0309
DOI:10.1016/j.ab.2003.08.032