Effects of pretreatment with verapamil on the toxicokinetics of soman in rabbits and distribution in mouse brain and diaphragm.
The effects of verapamil on the elimination of soman in rabbit blood and distribution in mouse brain and diaphragm by determining the concentration of P(-)soman using the chirasil capillary gas chromatographic analysis method were studied in order to study the effects of verapamil on the metabolic detoxification of soman. Verapamil (10 mg kg(-1), im, 30 min before soman administration) could significantly reduce the concentration of P(-)soman in rabbit blood at 15, 60, 90, 120, 180 and 240 s after soman injection (43.2 microg kg(-1), iv) as compared to soman-treated control animal respectively. Toxicokinetics parameters showed verapamil could increase clearance rate from 20.8+/-1.51 to 44.3+/-7.0 ml kg(-1)s(-1) and reduce AUC of P(-)soman from 2.08+/-0.151 to 0.996+/-0.172 mg s l(-1). For experiments in mice, verapamil could reduce the concentration P(-)soman in diaphragm from 74.7, 70.5, 88.7 to 41.1, 39.0, 49.3 ng 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. Verapamil accelerated the elimination of P(-)soman in the rabbits blood and reduced the distribution of P(-)soman in the mouse diaphragm.
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
Yu
Wei-Dong
WD
Song
Zheng-Yan
ZY
Qiao
Jian-Zhong
JZ
D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity; D002849:Chromatography, Gas; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D008658:Inactivation, Metabolic; D051379:Mice; D011817:Rabbits; D012999:Soman / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D014665:Vasodilator Agents; D012999:Soman; D014700:Verapamil