Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard.
10.1016/j.apsb.2014.08.002
- Author:
Pankaj VERMA
1
;
Rajagopalan VIJAYARAGHAVAN
2
Author Information
1. Department of Pharmaceutics, Anand College of Pharmacy, Keetham, Agra 282007, India.
2. Department of Pharmacology and Toxicology, Defence Research and Development, Establishment, Gwalior 474002, India.
- Publication Type:Journal Article
- Keywords:
Blood–plasma partitioning;
DRDE-07;
Pharmacokinetics;
Protein binding;
Sulfur mustard
- From:
Acta Pharmaceutica Sinica B
2014;4(5):394-401
- CountryChina
- Language:English
-
Abstract:
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.