A pharmacodynamic model for soman in the rat.
A pharmacodynamic model for inhibition of acetylcholinesterase (AChE) by soman was developed to describe the intertissue differences in AChE inhibition, the dose response of AChE to inhibition by soman, and the effect of differences in xenobiotic metabolism on soman toxicity. Based on the principles of physiological pharmacokinetics, this pharmacodynamic model consisted of a set of mass balance equations that included parameters for blood flow, tissue volumes, soman metabolism, tissue/plasma partition coefficients, initial AChE levels, and the rate constant for AChE inhibition. Sensitivity analysis of the model revealed that variation of the soman metabolism parameter in plasma was the most important determinant of variation in the inhibition of brain AChE by soman.
Maxwell
D M
DM
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Vlahacos
C P
CP
Lenz
D E
DE
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D012999:Soman