盐酸地尔硫卓缓释片在健康人体内的药动学和生物等效性.doc

盐酸地尔硫卓缓释片在健康人体内的药动学和生物等效性 朱运贵 顔素华（ 中南大学湘雅二医院临床药学研究室 长沙 410011） [摘要] 目的：研究盐酸地尔硫卓受试制剂和参比制剂的人体药动学和生物等效性。方法： 18名健康受试者随机交叉口服受试制剂和参比制剂，剂量均为120mg。血样经预处理后采用HPLC紫外检测法测定地尔硫卓浓度，以计算其主要药动学参数并进行统计学分析。结果：受试制剂和参比制剂的各主要药动学参数如下：Cmax 分别为（97.66(26.36） ng(mL-1 和（101.78(33.54） ng(mL-1, AUC0-t分别为（901.71 ( 270.84 ）ng(h(mL-1和(926.82 ( 277.02) ng(h(mL-1，AUC0-(分别为（974.58 ( 292.88） ng(h(mL-1和（995.85 ( 291.13） ng(h(mL-1，tmax分别为（3.4(0.8）h和（3.4(1.0）h。以AUC0-t计算的受试制剂的相对生物利用度为（97.5±10.2）%。结论：经方差分析及双单侧t检验结果显示受试制剂和参比制剂具有生物等效性。 关键词 盐酸地尔硫卓；高效液相色谱；药动学；生物等效性 Pharmacokinetics and bioequivalence of Diltiazem Hydrochloride Sustained release tablets in healthy volunteer Yang Su-hua ZHU Yun-gui ( 1. Clinic Pharmacy Research Laboratory, The Second Xiangya Hospital of Central south University, Changsha，410011 ChinaAbstract：Objective To research the pharmacokinetics and bioequivalence of Diltiazem Hydrochloride test and reference preparation in healthy volunteer. Methods A single oral dose of 120mg the test or the reference preparation was given to 18 healthy volunteers in a randomized two-period crossover study. Diltiazem concentration in plasma was determined by HPLC-UV. Main pharmacokinetic parameters were calculated and compared by statistic analysis. Results The pharmacokinetic parameters of test and reference preparation were as follows: Cmax were （97.66(26.36） ng(mL-1 and （101.78(33.54） ng(mL-1, AUC0-t were （901.71 ( 270.84 ）ng(h(mL-1 and (926.82 ( 277.02) ng(h(mL-1, AUC0-( were（974.58 ( 292.88） ng(h(mL-1 and（995.85 ( 291.13） ng(h(mL-1，tmax were（3.4(0.8）h and （3.4(1.0）h , respectively. The relative bioavalability of the test preparation was（97.5±10.2）%. Conclusion The result of ANOVA and two one-side t test show that the test and reference preparation are bioequivalent. Keywords Diltiazem Hydrochloride; HPLC; Pharmacokinetic; bioequivalence 地尔硫卓为苯并噻氮卓类钙拮抗药，是第三代抗心绞痛药和第四代抗心律失常药，主要用于治疗高血压、心绞痛和心律失常。本研究建立了HPLC法测定人血浆中地尔硫卓的浓度，并对其口服受试片剂和参比片剂的药动学及相对生物利用度进行了研究，为临床用药提供参考。 1 材料 岛津LC-2010A型液相色谱仪系统（日本岛津公司）；