摘要
DRDE-07,a newly synthesized amifostine analog currently under clinical investigation in a phase I trial,is a potent antidote against sulfur mustard toxicity.The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg.The physicochemical properties of DRDE-07,including solubility,pK a,Log P,plasma protein binding and plasma/blood partitioning,were determined to support the pharmacokinetic characterization.DRDE-07 concentration was determined by an HPLC-UV method.The profile of plasma concentration versus time was analyzed using a non-compartmental model.Plasma protein binding was assessed using ultrafiltration.DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels(C max)observed in less than 15 min.There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing.The plasma protein binding of DRDE-07 was found to be less than 25%at all concentrations studied.Plasma clearance of DRDE-07 is expected to be?1.5 fold higher than the blood clearance of DRDE-07.The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.
