甲硝唑经口腔吸收在大鼠体内的代谢动力学  

Metabolic Dynamics of Metronidazole Absorbed Through Mouth Cavity in Rats in Vivo

作　　者：辛显桐[1] 刘克明[1] 王虹[1] 张明月[1] 支秀珍[1] 

机构地区：[1]天津市卫生防病中心,300011

出　　处：《环境与健康杂志》2001年第2期80-82,共3页Journal of Environment and Health

基　　金：天津市卫生局科技基金资助项目 (99KY0 1 9)

摘　　要：目的　证实甲硝唑可经口腔吸收进入体内 ,了解其在体内的吸收和排泄情况 ,为含甲硝唑口腔卫生用品的安全性评价提供依据。方法　采用 SD大鼠 ,经结扎食管 30 min后口腔给予含 8%甲硝唑的牙膏 1mg/g(体重 ) ,于给药后0 .5、1、1.5、2、2 .5、3、4.5 h取血 ,应用高效液相色谱法测定血中甲硝唑含量 ,并进行药代动力学分析。结果　口腔给药后 ,0 .5 h血清中即可测得甲硝唑 6 .88μg/ml,说明甲硝唑可经口腔粘膜吸收。血清药 -时曲线拟合表明符合一级吸收一室模型 :C=10 .1419(e- 0 .43 3 7t- e- 1 0 .2 571 t) ,处理后的各项药代动力学参数为 :A=10 .144 9μg/ml;Ke=0 .4337h;Ka=10 .2 5 71h;L ag time=0 .3770 h;t1 / 2 (ka) =0 .0 6 76 h;t1 / 2 (ke) =1.5 984h;T(peak) =0 .32 2 0 h;C(max) =8.44 96 μg/ml;AUC=2 2 .40 43μg/(ml·h) ;CL/F(S) =1.42 93mg/(kg· h) ;V/F(C) =3.2 936 (mg/kg)。结论　甲硝唑可经口腔粘膜吸收进入血液。鉴于甲硝唑的遗传毒性作用 ,建议禁止或限制将甲硝唑加入口腔卫生用品中 ,以免人们长期接触产生不良后果。Objective To verify the absorption of metronidazole through mouth cavity in vivo,and understand the absorption and excretion of meltronidazole in vivo,and provide scientific bases for the safety assessment on oral health care products including metronidazole Methods The determination of contents of metronidazole in blood by HPLC and pharmacokinetics analysis were carried out in SD rats at the 0 5 h,1 h,1,5 h,2 h,2 5 h,3 h and 4 5 h after the oral exposure to the toothpaste containing 8% metronidazole after the 30 minute ligation of esophagus with a dose of 1 mg/kg body weight (BW) respectively Results 6 88 μg/ml metronidazole was found in serum of SD rats at the 0 5 h after the oral exposure,which indicated that metronidazole in toothpaste could be absorbed through mucous membrane The fited drug concentration in serum time curve accorded with the one compartment model of first grade absorption [C=10 1419(e-0 4337t-e-10 2571t)] The treated parameters of pharmacokinetics were as follows,A=10 1449 μg/ml,Ke=0 4337 h,Ka=10 2571 h;Lag time=0 3770 h,t1/2(ka)=0 0676 h,t1/2(ke)=1 5984 h,T(peak)=0 3220 h,C(max)=8 4496 μg/ml,AUC=22 4043 μg/(ml·h),CL/F(S)=1 429 3 mg/(kg·h),V/F(C)=3 2936 mg/kg Conclusion Metronidazole could be absorbed through oral exposure Due to the genotoxicity of metronidazole,it was proposed that the application of metronidazole in oral health care products should be prohibited and limited,to avoid causing adverse health effects of long term exposure to it

关 键 词：牙膏 甲硝唑 代谢动力学 安全性评价 口腔卫生用品 

分 类 号：R168[医药卫生—公共卫生与预防医学] R996