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Influence of cimetidine on the toxicity and toxicokinetics of diazinon in the rat

Lyons Poisons Center and Department of Pharmacology and Medical Toxicology, INSERM U80, Alexis Carrel Faculty of Medicine, 69008 Lyons, France

CI Evreux-Gros

Lyons Poisons Center and Department of Pharmacology and Medical Toxicology, INSERM U80, Alexis Carrel Faculty of Medicine, 69008 Lyons, France

J. Descotes

Lyons Poisons Center and Department of Pharmacology and Medical Toxicology, INSERM U80, Alexis Carrel Faculty of Medicine, 69008 Lyons, France

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, ip) 1 and 24 h prior to diazinon applica tion (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.

Key Words: diazinon • toxicokinetics • acute toxicity • cimetidine • interaction

Human & Experimental Toxicology, Vol. 15, No. 5, 391-395 (1996)
DOI: 10.1177/096032719601500505


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