Effect of poisoning by soman (pinacolyl methylphosphono‐fluoridate) on the serum half‐life of the cholinesterase reactivator hi‐6 in mice

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Abstract
The effect of fasting, atropine, and poisoning by an organophosphae anticholinesterase soman (pinacolyl methylphosphonofluoridate) on the pharmacokinetics of the acetylcholinesterase oxime reactivator HI‐6 (CAS Reg. No. 34433‐31‐3; l‐(((4‐(aminocarbonyl) pyridinio)methoxy)methyl)‐2‐(hydroxyimino)methyl) pyridinium di‐chloride) was investigated. Pharmacokinetic parameters (elimination half‐life, volume of distribution, clearance rate) were determined for the following groups: (1) a 20 and 50 mg kg−1 dose of HI‐6; (2) a 50 mg kg−1 dose of HI‐6 after fasting for 18 h (water ad lib); (3) a 50mg kg−1 dose of HI‐6 at 0, 4, and 24h after atropine (17.4mg kg−1, i.p.) and soman (287μg kg−1, s.c); and (4) a 50mg kg−1 dose of HI‐6 at 0 and 4h after soman (100 μg kg−1, s.c). Fasting increased significantly (p(t½) and tended to increase the volume of distribution (Vd) and decrease the clearance rate (CL). Following soman (287 μg kg−1) poisoning the UA of HI‐6 increased from 8‐6 min to 21‐6 min and the Vd increased to 0.731 kg−1. At the lower soman dose (100 μg kg−1) no significant effect on HI‐6 pharmacokinetics was found. Atropine (17.4μg kg−1: i.p.) pretreatment increased the t½ and CL while having no effect on the Vd. By 24 h the pharmacokinetic parametes of HI‐6 in the various treatment groups were not significantly different from the control group. The changes in the pharmacokinetics of HI‐6 following soman and atropine are probably the result of haemodynamic changes.