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 inhibitio n, were potentiated by pretreating rats with cimetidine (80 mg kg(-1), ip) 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 concentra tion-time curve following cimetidine. 4 These results indicate that a major cause of the potentiation of diazinon may be related to the incr ease in the amount of diazinon in the systemic circulation as well as in the brain.