国产盐酸西替利嗪片的药代动力学研究

Pharmacokinetics of Domestic Cetirizine Hydrocloride Tablet in 11 Healthy Volunteers

目的 :建立测定国产盐酸西替利嗪 (西可韦 )血药浓度的方法并进行人体药代动力学研究。方法 :采用反相高效液相色谱法 ,以盐酸普罗帕酮为内标 ;色谱柱 :WaterssymmetryC18 不锈钢柱 (3 9mm×150mm ,5μm) ;流动相 :乙腈 -0 02mol/L磷酸二氢钠 -三乙胺 (50∶50∶0 16 ,V/V) ,含十二烷基硫酸钠 (SDS)4 0mmol/L ;流速 :1 0ml/min ;检测波长 :229nm。测定11名健康男性志愿者单剂量口服西可韦片10mg 的血浆中药物浓度。结果 :线性范围为12 5～800ng/ml,最低检测限为5ng/ml,提取回收率>75 %。11名志愿者的血药浓度数据经3p87软件拟合 ,符合血管外给药二室模型 ,其主要药代动力学参数为 :Cmax=(429 00±108 80)ng/ml,Tmax= (0 91±0 40)h ,K10= (0 18±0 04)/h ,以梯形法计算的AUC0～36= (3312 72±682 39)ng/(ml·h)。结论 :本方法结果准确 ,灵敏度高 ,能满足人体药代动力学研究的需要 ;西可韦主要药代动力学参数与国内、外文献报道一致 。

OBJECTIVE:A reversed-phase high performance liquid chromatography(RP-HPLC)method was established to study the pharmacokinetics of cetirizine hydrocloride tablet in 11 healthy male volunteers METHODS:Waters HPLC instrument was used with the Waters symmetry C18 steeless column(3 9mm×150mm,5μm) The mobile phase was composed of acetonitrile-0 02mol/L sodium hydrogen diphosphate-triethylamine(50∶50∶0 16,V/V),which contained 4 0mmol/L sodium dodecyl sulphate Flow rate was 1 0ml/min Detection wavelength was 229nm Propafenone was taken as internal standard A single 10mg oral dose of cetirizine hydrocloride tablet was given to 11 healthy male volunteers Cetirizine concentration was assayed in plasma RESULTS:The standard curve of cetirizine hydrocloride was linear in the range of 12 5～800ng/ml The minimum detection limitation was 5ng/ml The extraction recovery was more than 75% A two-compartment open pharmacokinetic model was adapted in cetirizine plasma concentration-time data analysis The main pharmacokinetic parameters were as follows:Cmax=(429 00±108 80)ng/ml,Tmax=(0 91±0 40)h,AUC0～36(calculated by trapezoid method)=(3 312 72±682 39)ng/(h·ml) CONCLUSION:The method was accurate,sensitive and reliable It is applicable to determine the concentration of cetirizine hydrocloride in human plasma;The main pharmaconetic parameters of the domestic cetirizine hydrocloride tablet were similar to those reported at home and abroad,so it could be extensively used in clinic