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 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.
Busker
R W
RW
Research Group of Pharmacology, Prins Maurits Laboratory, TNO, Rijswijk, The Netherlands.
Zijlstra
J J
JJ
Philippens
I H
IH
Groen
B
B
Melchers
B P
BP
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002144:Callithrix; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009482:Neurophysiology; D010091:Oximes; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D012999:Soman / Q000008:administration & dosage / Q000633:toxicity*
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D010091:Oximes; D011726:Pyridinium Compounds; D001285:Atropine; D012999:Soman; D002802:Cholinesterases; C022870:asoxime chloride