Effects of pretreatment with 8018 on the toxicokinetics of soman in rabbits and distribution in mice.
The effects of 8018 [3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyl-ethoxy)quinuclidine] on the elimination of soman in rabbits blood and distribution in mice brain and diaphragm were investigated using the chirasil capillary gas chromatographic analysis method. In all experiments, the concentration of P(+)soman was below the detection limit (<0.1 ng x mL(-1)). 8018 (1 mg x kg(-1), im, 10 min pre-treated) could significantly reduce the concentration of P(-)soman in rabbit blood from 53.6 +/- 13.3 to 26.2 +/- 9.70 ng x mL(-1) blood as compared to soman-treated control animal at 15 s following soman injection (43.2 microg x kg(-1), iv). Toxicokinetic parameters showed 8018 could increase clearance (CL((S))) from 20.8 +/- 1.54 to 38.2 +/- 15.3 mLx kg(-1) x s(-1) and reduce AUC of P(-)soman from 2.08 +/- 0.151 to 1.30 +/- 0.564 mg x s x L(-1). 8018 could reduce the concentration P(-)soman in diaphragm from 74.7, 70.5, 88.7 ng x g(-1) to 54.5 45.6, 50.0 ng x g(-1) at the time of 30, 90, 120 s after intoxication of soman subcutaneously vs. soman control respectively, but it had no influence on the concentration of free P(-)soman in brain. Isotope trace experiments showed that it could significantly increase the distribution amount of bound [3H]soman in mice plasma and small intestine during 0-120 min after mice received [3H]soman (0.544 GBq.119 microg x kg(-1), sc) compared to soman control group.
Li
Jin-Tong
JT
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China. leejohnton@yahoo.com
Ruan
Jin-Xiu
JX
Zhang
Zhen-Qing
ZQ
Yuan
Shu-Lan
SL
Yu
Wei-Dong
WD
Song
Zheng-Yan
ZY
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D019540:Area Under Curve; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity*; D002849:Chromatography, Gas; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D051379:Mice; D011812:Quinuclidines / Q000494:pharmacology*; D011817:Rabbits; D012999:Soman / Q000493:pharmacokinetics* / Q000633:toxicity*; D014018:Tissue Distribution
C475828:3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyl-ethoxy)quinuclidine; D000931:Antidotes; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D007202:Indicators and Reagents; D011812:Quinuclidines; D012999:Soman