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目的 :考察维拉帕米对梭曼兔的毒代动力学及小鼠脑与膈肌分布的影响 ,探索维拉帕米对梭曼代谢解毒作用机制。方法 :大进样量气相色谱仪及手性毛细管柱氮磷检测器测定兔静脉染毒后血中及小鼠皮下染毒后脑与膈肌中游离C(± )P(_)梭曼。结果 :维拉帕米 (10mg kgim ,预给药 0 .5h) ,在中毒后 15 ,6 0 ,90 ,12 0 ,180及 2 4 0s可明显降低血液中游离C(± )P(_)梭曼浓度。维拉帕米使C(± )P(_)梭曼的CL由 (2 0 .8± 1.5 )ml (kg·s)显著增加到 (4 4 .3±7.0 )ml (kg·s) ;使AUC由 (2 .0 8± 0 .15 )mg·s L显著下降到 (0 .996± 0 .172 )mg·s L。维拉帕米预给药在小鼠皮下梭曼染毒后 30 ,90及 12 0s时 ,能使膈肌中游离C(± )P(_)梭曼的浓度由 74 .7,70 .5 ,88.7ng g降低到 4 1.1,39.0 ,4 9.3ng g。但在以上时间点对脑中游离C(± )P(_)梭曼的浓度却没有显著的影响。结论 :维拉帕米能促进血中游离C(± )P(_)梭曼的消除 ,并降低靶器官膈肌中的分布 ,从而促进了梭曼的代谢解毒。
OBJECTIVE: To investigate the influence of verapamil on the toxicokinetics of toman rabbit and the distribution of brain and diaphragm in mice, and explore the mechanism of verapamil on soman metabolism and detoxification. Methods: The free C (±) P (_) soman in the brain and diaphragm muscle was measured in the blood of the rabbit vein and the mouse after subcutaneous injection of the drug by a large sample volume gas chromatograph and a chiral capillary column nitrogen and phosphorus detector. Results: Verapamil (10 mg kgim, pretreatment 0.5 h) significantly reduced free C (±) P (_) in blood after 15, 60, 90, 120, 180 and 240 s after poisoning Soman concentration. Verapamil significantly increased the CL of C ± P () soman from (20.8 ± 1.5) ml (kg · s) to (44.3 ± 7.0) ml (kg · s). The AUC decreased from (2.08 ± 0.15) mg · s L to (0.996 ± 0.172) mg · s-L. The concentration of free C (±) P (_) soman in the diaphragm at 30, 90 and 12 s after subcutaneous soman administration in mice was increased from 74.7, 70.5, 88.7 ng g to 4 1.1, 39.0, 4 9.3 ng g. However, there was no significant effect on the free C (±) P (_) soman concentration in the brain at the above time points. Conclusion: Verapamil can promote the elimination of somatic C (±) P (superscript +) soman in blood and decrease the distribution of target organ diaphragms, which promotes the metabolic detoxification of soman.