家兔敌敌畏代谢动力学与胆碱酯酶抑制毒效动力学的关系

Relationship between toxicokinetics and toxicodynamics on cholinesterase inhibition of dichlorvos in rabbits

用比色法测定全血中敌敌畏浓度求得其ｉｖ及ｉｇ的房室模型及系列毒代动力学参数．ｉｖ时呈三房室分布，ｔ１／２β＝１７２ｍｉｎ，Ｖｃ＝０．６１Ｌｋｇ－１；ｉｇ时呈二房室分布，ｔ１／２β＝１２６ｍｉｎ，ｋａ＝０．４９ｍｉｎ－１，Ｆ＝０．３９０．用Ｅｌｍａｎ氏法测定全血胆碱酯酶活性求得敌敌畏的毒效动力学参数．证明两种动力学的曲线型基本一致且同步变化，但毒效动力学曲线的斜率较小．敌敌畏ｉｇ中毒时ｉｖ碘解磷定，对敌敌畏毒代动力学没有影响，但对毒效动力学有明显影响，使斜率增加约３倍．离体实验敌敌畏抑制全血胆碱脂酶活性的浓度－效应关系与在体者基本一致，故离体的浓度－效应关系配合以在体的时间－效应关系，可推测出在体的时间－浓度关系．

The relationship between toxicokinetics and toxicodynamics on cholinesterase(ChE) inhibition of dichlorvos (DDVP),and the influence of pralidoxime iodide (PAM) on this relationship were investigated. Blood concentration of DDVP was determined with 4-(4-nitrobenzyl)-pyridine colorimetric method and blood ChE activity aws analyzed by Ellman's method. The principal toxicokinetic parameters are as follows:when iv 3.23mg·kg -1 ,first-order elimination kinetics,three compartment model,t 1/2 β=172min,V c=0.61L·kg -1 ;when ig 12.9mg·kg -1 ,also first order kinetics ,two compartment model,t 1/2 β=126min,k a=0.49min -1 ,F=0.390. The curves are same shaped in toxicokinetics and toxicodynamics,but the slop of the former curve is larger than the latter one,e.g. when ig administration,the regression analysis of the points at the distribution and elimination phaes of toxicokinetics with the corresponding points of toxicodynamics shows b=0.434,r=.0.996.PAM(50mg·kg -1 iv at 11th min)does not affect the toxicokinetis of DDVP(12.9mg·kg -1 ,ig),but it changes the ChE inhibition toxicodynamics of DDVP with about 2-3 folds increase of the slop of the curve(b increased from 0.434 to 1.427). The concentration-effect relationship of DDVP inhibiton on ChE activity in vitro is basically identical with in vivo. Therefore it is concluded that the time-concentration relation ship in vivo can be estimated by using the time-effect relationship in vivo and the concentration-effect relationship in vitro of DDVP.