Add time:08/13/2019         Source:sciencedirect.com

Thiophosphate insecticides—fenitrothion, diazinon and methylparathion—inhibit hepatic drug-metabolizing enzyme activity, which was assayed using aminopyrine and aniline as substrates. About 50 per cent inhibition was noted 4 hr after the injection of 25 mg/kg of fenitrothion into mice. The addition of thiophosphates to a microsomal drug-metabolizing enzyme system in vitro also produced an effective inhibition: IC50 was ca 10−5 M for fenitrothion. DDVP and an oxygenated metabolite of fenitrothion did not show any inhibiting effect either in vitro or in vivo. The inhibition in vitro was competitive, while the kinetics of inhibition in vivo appeared to be noncompetitive. Drug metabolism by a rat liver preparation was also inhibited by thiophosphate in vitro, but treatment of male rats in vivo resulted in little inhibition. The responses of female rats were similar to those of mice. The administration of fenitrothion to mice prolonged the hexobarbital sleeping time and suppressed the oxidative metabolism of parathion in liver preparations.

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