Kinetics and metabolism of physostigmine in rat in the presence of soman

The effect of soman (105 μg/kg; 1.5 LD50 s.c.) administration on pharmacokinetics and metabolism of 3H-physostigmine (Phy) was studied in rats. The rats were pretreated with either Phy 100 μg/kg i.v. or 500 μg/kg i.m., 5 or 15 min prior to soman administration. Phy and metabolites were determined in plasma and brain by HPLC. The half-life of Phy in plasma after i.v. administration was 15.5 min both in the presence and absence of soman, however the t/sub 1/2/ in brain was 11 min and 13 min, respectively. Clearance was 71.4 ml/min/kg in the Phy treated rat and 90 ml/min/kg in the presence of soman. The half-life of Phy in plasma was 18 min and 17 min, and in brain 17 min and 15 min, respectively in the absence and presence of soman after i.m. dose of Phy. Clearance after Phy treatment was 85.2 mlmin/kg however in the presence of soman, it was 66.7 ml/min/kg. Phy was slightly less metabolized to eseroline and two other metabolites, M1 and M2, in the presence of soman after i.v. as well as after i.m. administration in plasma and brain. The soman administration does not change the pharmacokinetics of Phy by the two different dosages and routes of administration