title: Diazinon toxicokinetics, tissue distribution and anticholinesterase activity in the rat.
abstract: 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.
authors.affiliation: Department of Pharmacology and Medical Toxicology, INSERM U80, LYON-RTH Laennec Faculty of Medicine, France.
authors.forename: H X
authors.initials: HX
authors.lastname: Wu
authors.forename: C
authors.initials: C
authors.lastname: Evreux-Gros
authors.forename: J
authors.initials: J
authors.lastname: Descotes
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001682:Biological Availability; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D003976:Diazinon / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D007306:Insecticides / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000110:Acetylcholinesterase; D003976:Diazinon