COMPARISON OF THE EFFICACY OF SINGLE OR REPEATED HI-6 TREATMENT FOLLOWING SOMAN POISONING IN GUINEA-PIGS AND MARMOSET MONKEYS

The therapeutic efficacy of single or repeated doses of HI-6, together with atropine, against soman poisoning were compared both in guinea p igs and in marmoset monkeys. In addition, the pharmacokinetics of HI-6 were determined after single or repeated injections. Both single and repeated HI-6 injections protected guinea pigs effectively against 2 x LD(50) soman. The plasma levels of HI-6 after single HI-6 injection f itted a one-compartment elimination model. The plasma levels of HI-6 f ollowing repeated injections were in accordance with those predicted u sing the data obtained after single HI-6 injection. No evidence was fo und for any disturbance of the HI-6 elimination in guineapigs followin g soman intoxication. Marmosets were intoxicated with 2 x LD(50) soman (s.c.), followed after 1 min by i.m. injections of atropine and HI-6. One and 2 h later, four animals received additional HI-6 injections. The pharmacokinetics of HI-6 in plasma, after single and repeated HI-6 injections were similar to those found in the guinea pig. Furthermore , repeated HI-6 injections protected effectively against soman: four o ut of four animals survived, in fair condition. In contrast, only one out of four animals receiving single HI-6-treatment fully recovered wi thin a few days. Two animals died, the fourth animal survived, but had to be euthanized 3 weeks after intoxication.