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

Abstract

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.