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.