Mechanism of Action and Pharmacokinetics of Physostigmine in Relation to Acute Intoxication by Organofluorophosphate. Report for September 1, 1985-August 31, 1986

摘要

The time course of Phy and metabolites in plasma, brain, muscle, and liver was studied after pretreatment of phy (100 micrograms/kg i.m. or 500 micrograms/kg i.m.) then soman challenge (105 micrograms/kg s.c.). The brain to plasma ration of Phy is almost the same, and there is no appreciable change in the metabolism and pharmacokinetics of Phy in the presence or absence of soman. The time course of BuChE and ChE activity in plasma, brain and muscle after soman challenge shows a large drop in enzyme activity (2-5% in plasma and brain and 62% in muscle) at 15 min. This activity does not recover over the times studied. Pretreatment with Phy (100 micrograms/kg i.v.) and then soman challenge produces a similar drop in ChE activity with a slow recovery indicating a very little or no protective effect of Phy. Pretreatment with Phy (500 micrograms/ kg i.m.) and then soman challenge shows some protective effect on plasma BuChE activity (25-30%), brain and muscle ChE activity (35% and 76%, respectively). These results indicate some protective effect of pretreatment of Phy on ChE activity. The time course of metabolism and pharmacokinetics of Phy in plasma, brain, liver, and muscle after Phy administration (650 micrograms/kg oral) indicate a very small amount of parent drug was present in plasma and tissue. Keywords: Antidotes. (aw)