In Vitro Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) Metabolism in Human Liver.

摘要

This project is the first to investigate RDX metabolism in human liver. RDX metabolism was screened in human liver tissues including S9 preparations, microsomes, hepatocytes and several recombinant CYP450 isoforms under aerobic, anaerobic and oxygen reduced conditions. RDX metabolism was also conducted in several animal liver microsomes to compare with human liver microsomes loss of the parent compound (RDX) was determined at 30 and 180 minutes of the incubation and ranked as human (46.6% & 51.8%)> rat (40.1% & 47.2%)> monkey (34.6% & 35.7%)> Pig (25.5% & 33.7%)> rabbit (11.6% & 18.0). The data is used to establish Physiologically-based pharmacokinetic (PBPK) models for human useful in risk assessment. Further characterization of the profiles of RDX in vitro metabolism in human and animal liver tissues is proposed. This study developed an in vitro metabolic model which mimics in vivo physiological condition and will be useful in the evaluation of human metabolic fate for novel energetics such as replacement formulations for RDX and for other toxic TICs/TIMs.