Wu H X, Evreux-Gros C, Descotes J
Department of Pharmacology and Medical Toxicology, INSERM U80, LYON-RTH Laennec Faculty of Medicine, France.
Biomed Environ Sci. 1996 Dec;9(4):359-69.
The toxicokinetics, tissue distribution, and anticholinesterase (antiChE) activity of diazinon were investigated in the rat. Plasma concentrations most adequately fitted a two-compartment open model after i.v. administration of 10 mg/kg and a one-compartment model after oral administration of 80 mg/kg. Diazinon elimination half-life following i.v. and oral dosing was 4.70 and 2.86 h, respectively. The oral bioavailability was found to be low (35.5%). Hepatic extraction ratios after i.v. administration of 5 or 10 mg/kg were 54.8% and 47.7%, respectively, suggesting that low systemic oral bioavailability can be explained by a first-pass effect in the liver. Diazinon was found to be approximately 89% protein-bound in plasma within the concentration range 0.4-30 ppm. The highest concentration of diazinon after i.v. administration was found in the kidneys, when comparing to liver, kidney, brain. Both red blood cell (RBC) acetylcholinesterase (AChE) and plasma ChE activities were inhibited rapidly (44% and 17% at 10 min, and 36% and 13% min for i.v. and oral administration, respectively), but inhibition of RBC AChE was greater than that of plasma ChE.
在大鼠体内研究了二嗪农的毒代动力学、组织分布及抗胆碱酯酶（antiChE）活性。静脉注射10mg/kg后，血浆浓度最适合二室开放模型；口服80mg/kg后，血浆浓度最适合一室模型。静脉注射和口服给药后，二嗪农的消除半衰期分别为4.70小时和2.86小时。发现口服生物利用度较低（35.5%）。静脉注射5mg/kg或10mg/kg后，肝脏提取率分别为54.8%和47.7%，这表明口服生物利用度低可由肝脏首过效应来解释。在0.4 - 30ppm浓度范围内，二嗪农在血浆中的蛋白结合率约为89%。静脉注射后，与肝脏、肾脏、脑相比，在肾脏中发现二嗪农的浓度最高。红细胞（RBC）乙酰胆碱酯酶（AChE）和血浆胆碱酯酶（ChE）活性均迅速受到抑制（静脉注射和口服给药10分钟时分别抑制44%和17%，30分钟时分别抑制36%和13%），但红细胞AChE的抑制程度大于血浆ChE。
