title: Effects of pretreatment with verapamil on the toxicokinetics of soman in rabbits and distribution in mouse brain and diaphragm.
abstract: 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.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China. leejohnton@yahoo.com
authors.forename: Jin-Tong
authors.initials: JT
authors.lastname: Li
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Ruan
authors.forename: Zhen-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yu
authors.forename: Zheng-Yan
authors.initials: ZY
authors.lastname: Song
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Qiao
mesh_terms: 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*
chemical_list: D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D014665:Vasodilator Agents; D012999:Soman; D014700:Verapamil