茶苯海明口崩片的人体药代动力学及相对生物利用度研究

Study on pharmacokinetics and relative bioavailability of rapid oral disintegrating tablet of dimenhydrinate

目的：比较茶苯海明口崩片和普通市售片的人体内药代动力学及相对生物利用度。方法：8名健康志愿者均分为2组，分别为口含单剂量茶苯海明口崩片（25mg／片）和口服茶苯海明普通市售片（25mg／片）后，分别服药前和服药后用高效液相色谱法测定血药浓度。色谱条件：色谱柱：Nova-Pak C18（4μm，3．9mm×150mm），保护柱：Nova—Pak C18 （4μm，3．9mm×30mm），流动相为甲醇：三乙胺缓冲液（磷酸4ml，三乙胺7ml，加50％甲醇稀释至1000ml，用磷酸调节pH3．2），流速1．0ml／min，检测波长225nm，进样量20μl，室温。进行口崩片与普通市售片的药代动力学和生物利用度研究。结果：茶苯海明在人空白血浆中的标准曲线方程：C=0．0044A＋4．745，R^2=0．996，在5～500ng／ml的浓度范围内线性良好。最低检测限2ng／ml。平均回收率为（90．55±4．69）％，RSD=0．041％。低、中、高3种浓度的日内RSD分别．为9．27％，4．93％，2．95％（n=5）。日间RSD分别为9．97％，3．81％，3．06％（n=5）。取血样3ml处理后进样，两剂型血药浓度有显著差异，口崩片为：茶苯海明血药浓度一时间曲线下面积（AUC）=（602．04±113．82）ng·h·ml^-1，峰浓度（Cmax）=（95．86±21．28）ng·ml^-1，达峰时间（TPeak）=（1．8±0．32）h，市售片的药动学参数为：AUC=（342．73±84．96）ng·h·ml^-1，Cmax=（46．34±10．32）ng·ml，Tpeak=（2．65±0．24）h，口崩片与普通片的生物利用度的差异有统计学意义（P〈0．01），相对生物利用度为175．66％。结论：所研制的口崩片能显著提高茶苯海明的生物利用度。

Objective：To compare the pharmacokinetics and relative bioavailability of rapid oral disintegrating tablet of dimenhydrinate （RODTD） and those of market available tablet of dimenhydrinate （DMH）. Methods： Eight healthy volunteers were evenly randomized into 2 groups, one group received RODTD （25 mg） and the other received available market tablet of dimenhydrinate （25 mg）. The blood levels of DMH were determined by high performance liquid chromatography （HPLC） before and after drug administration in 2 groups. Chromatography conditions were： Nova-Pak Clsas chromatographic column, methanol triethylamine buffer （1 ： 1）, flow rate： 1.0 ml/min, detection wavelength： 225 nm, and room temperature. The pharmacokinetics and relative bioavailability of RODTD and market available tablets were investigated. Results： The standard curve of DMH in the blank plasma was linear within the range of 5-500 ng/ml, with the regression equation being C=0. 004 4 A＋4. 745 and R^2 =0. 996. The limit of detection was 2 ng/ml; the average recovery rate was （90.55±4.69） % and the RSD was 0. 041%. The intra-day derivations of 3 different concentrations （low, middle, and high） of plasma were 9.27%, 4.93%, and 2.95%, respectively （n = 5）, and the inter-day derivations were 9.97 %, 3.81%, and 3.06 %, respectively （ n = 5 ）. Blood samples （3 ml） were subjected to HPLC assay and significant difference was found between the 2 forms of DMH. The pharmacokinetic parameters of RODTD were： AUC= （602.04±113.82） ng . h. ml^-1 ,Cmax= （95. 86±21. 28） ng.ml^-1 ,and Tpeak = （1. 8±0. 32） h, the pharmacokinetic parameters of market available tablets were： AUC = （342.73±84.96） ng.h.ml^-1 , Cmax = （46.34±10.32） ng.ml^-1 ,and Tpeak = （2. 65±0. 24） h. Statistical analysis showed there was significant difference in the relative bioavailability of 2 forms of DMH（P〈0.01）. The relative bioavailability of RODTD to market tablet was 175.66%. Conclusion： The developed RODTD can obviously increase the relative bioavailability of DMH.