Busker_1996_Toxicology_112_183

The therapeutic efficacy of single or repeated doses of HI-6, together with atropine, against soman poisoning were compared both in guinea pigs 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 LD50 soman. The plasma levels of HI-6 after single HI-6 injection fitted a one-compartment elimination model. The plasma levels of HI-6 following repeated injections were in accordance with those predicted using the data obtained after single HI-6 injection. No evidence was found for any disturbance of the HI-6 elimination in guinea pigs following soman intoxication. Marmosets were intoxicated with 2 x LD50 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 out of four animals survived, in fair condition. In contrast, only one out of four animals receiving single HI-6-treatment fully recovered within a few days. Two animals died, the fourth animal survived, but had to be euthanized 3 weeks after intoxication.