氟虫腈及其砜化物在兔体内的毒物代谢动力学  

Toxicokinetics of fipronil and fipronil sulfone in rabbits

作　　者：胡国新[1] 陈晓宇[2] 周红宇[1] 邱相君[3] 陈冰冰[1] 卢中秋[2] 

机构地区：[1]温州医学院药理学教研室,浙江温州325027 [2]温州医学院附属第一医院急诊室,浙江温州325027 [3]河南科技大学医学院药理学教研室,河南洛阳471003

出　　处：《中国药理学与毒理学杂志》2006年第4期356-360,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的建立兔血浆中氟虫腈及其砜化物的高效液相色谱(HPLC)检测法,并研究其在兔体内的毒物代谢动力学,为氟虫腈中毒的临床诊断与治疗提供依据。方法氟虫腈3 m.gkg-1兔耳缘静脉注射后不同时间取血,采用高效液相色谱法检测血浆中氟虫腈及其砜化物的浓度,计算毒动学参数。结果氟虫腈的毒动学参数:k10为(2.08±0.83)h-1,k12为(0.34±0.07)h-1,k21为(0.27±0.05)h-1,cmax为(3.48±0.52)m.gL-1;t1/2α为(0.31±0.11)h;t1/2β为(3.25±0.59)h;AUC为(4.96±1.22)mg.h.L-1;C l为(1.49±0.44)L.h-1;V1为(0.67±0.15)L.kg-1;V为(2.62±0.65)L.kg-1;砜化物的毒动学参数:cmax为(1.10±0.10)m.gL-1;tmax为(6.08±1.94)h;t1/2ke为(81.3±4.8)h;AUC为(136±16)mg.h.L-1;C l为(0.05±0.005)L.h-1;Vd为(2.32±0.11)L.kg-1。结论氟虫腈静脉给药的毒物代谢动力学符合二室模型;其砜化物的毒物代谢动力学符合一室模型。氟虫腈砜化物的半衰期明显长于氟虫腈。AIM To study the toxicokinetics of fipronil and fipronil sulfone in rabbits and offer evidence for clinical diagnosis and treatment of fiproni intoxication. METHODS With diaze pam as the internal standard, fipronil and fipro- nil sulfone were detected by UV detector at 276 nm with the Hypersil-ODS C18 column and acetonitrile-methanol-water （ 26： 24： 50, V/V/V） as the mobile phase at a flow rate of 1.0 mL·min^-1. Six male rabbits were involved in the study and injected with fipronil 3 mg·kg^-1. The plasma fipronil and fipronil sulfone concentrations were determined by HPLC and calculated by 3P87 pharmacokinetics program. RESULTS After intravenous injection of a single dose of 3 mg·kg-^1 fipronil to rabbits, the toxicokinetical parameters of fipronil were as follows： κ10, （2.08±0.83） h^-1; κ12, （0.34± 0.07）h^-1 κ21, （0.27±0.05）h^-1 （3.48±0.52）mg·L^-1, t1/2α,, （0.31±0.11） h, t1/2β, （3.25±0.59） h, AUC, （4.96± 1.22）mg·h·L^-1, Cl, （1.49±0.44）L·h^-1,V1, （0. 67 ±0. 15）L·kg^-1, V, （2. 62 ± 0.65 ） L·kg^-1. The toxicokinetical parameters of fipronil sulfone were as follows ： cmax, （ 1.10 ± 0.10）mg·L^-1; tmax, （6.08 ±1.94） h; t1/2κe, （81.3 ±4.8）h; AUC, （136 ±16）mg·h·L^-1; Cl,（0.05 ±0.005）L·h^-1, h^-1 （2.32 ±0.11 ） L·kg^-1. CONCLUSION Following intravenous injection administration, the kinetics of fipronil is fitted to two-compartment model and fipronil sulfone is fitted to one-compartment model. The haft life of fipronil sulfone is longer than that of fipronil.

关 键 词：氟虫腈 氟虫腈砜化物 色谱法 高压液相 毒代动力学 

分 类 号：R114[医药卫生—卫生毒理学]