Influence of cimetidine on the toxicity and toxicokinetics of diazinon in the rat.
1. The influence of cimetidine on diazinon toxicity and toxicokinetics was investigated in male Wistar rats. 2. The acute toxicity of diazinon, as well as brain acetylcholinesterase and carboxylesterase inhibition, were potentiated by pretreating rats with cimetidine (80 mg kg-1, i.p.) 1 and 24 h prior to diazinon application (50 mg kg-1, i.p.). 3. Comparison of toxicokinetic parameters between control and cimetidine-treated animals, showed a significant decrease in diazinon total body clearance and a marked increase in the area under the plasma concentration-time curve following cimetidine. 4. These results indicate that a major cause of the potentiation of diazinon may be related to the increase in the amount of diazinon in the systemic circulation as well as in the brain.
Wu
H X
HX
Lyons Poisons Center, INSERM U80, Alexis Carrel Faculty of Medicine, France.
Evreux-Gros
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Descotes
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D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D002927:Cimetidine / Q000008:administration & dosage / Q000633:toxicity*; D003976:Diazinon / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D000110:Acetylcholinesterase; D003976:Diazinon