Diazinon Toxicokinetics,Tissue Distribution and Anticholinesterase Activity in the Rat
1996
The toxicokinetics.tissue distribution,and anticholinesterase(antiChE) activity of diazinon were investigated in the rat.Plasma concentrations most adequalely fitteda two-compartment open model after iv administration o 10mg/kg and a one-compartment model after oral administration of 80mg/kg.Diazinon elimination half-life following iv and oral dosing was 4.70and 2.86h,respectively.The oral bioavailability was found to be low(35.5%).Hepatic extraction ratios after iv administration of 5 or 10mg/kgwere 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% proteinby a first-pass effect in the live.Diazinon was found to be approximately 89% proteinbound in plasma within the concentration range 0.4-30ppm.The highest concentration of diazinon after iv administration was found in the kidneys,when comparing to liver, kindney,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% at 30min for iv and oral administration,respectively),but inhibition of RBC AChE was greater than that of plasma ChE.
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