西酞普兰片剂的人体生物等效性研究

Bioequivalent study of citalopram tablets

目的:研究国产氢澳酸西酞普兰片剂在健康人体内的药动学和与进口参比片剂比较的生物等效性。方法:24例健康男性志愿者单剂量随机交叉口服20 mg西酞普兰国产或进口片剂,血浆样品经碱化后用乙醚提取,再经酸化反提取处理。采用反相HPLC-RF法测定血浆中西酞普兰浓度,检测波长:激发波长240 nm,发射波长305 nm。采用3P97药动学程序计算药动学参数和相对生物利用度,并对参数进行方差分析和双单侧t检验。结果:西酞普兰受试片和参比片的主要药动学参数:Cmax分别为(26．99±4．68)和(27．27±4．16)μg·L-1;Tmax分别为(4．48±1．53)和(4．13±1．25)h;t1/2分别为(39．62±10．49)和(37．99±7．45)h;AUC0→∞分别为(1 459．4±480．9)和(1 388．4±1402．5)μg·h·L-1。国产片剂的相对生物利用度为(105．4±24．4)％,统计学结果表明两种片剂生物等效。结论:西酞普兰国产和进口片剂具有生物等效性。

Objective：To compare the pharmacokinetic profiles of domestic citalopram hydrobromide tablets （test samples） with imported citalopram hydrobromide tablets （reference samples）. Methods：24 healthy male volunteers were randomized to administer orally a single crossover dose of either test or reference citalopram hydrobromide tablet 20 mg. The blood samples of the volunteers were alkalinized and then acidized to extract the blood citalopram samples with ether. The plasma citalopram samples level was determined by reverse phase HPLC with a fluorescence-detection at Ex240 nm and Em305 nm. The pharmacokinetics parameters and relative bioavailability were calculated using 3P97 pharmacokinetics software. Variance analysis and two-one sided t test were performed. Results： The main pharmacokinetic parameters of test and reference citalopram tablets were as follows ： Cmax （26.99 ± 4.68 ） vs. （27.27 ± 4. 16） μg·L^-1,Tmax （4.48 ±1.53） vs. （4. 13 ±1.25）h, t 1/2 （ 39. 62 ±10. 49） vs. （37.99±7.45） h, AUC0→∞ （1459.4 ±480.9） vs. （1388.4 ±402.5）μg·h. L^-1. The relative bioavailability of test citalopram hydrobromide tablets was （ 105.4 ± 24.4） %. No statistical difference of the pharmacokinetic parameters was found for the test and reference samples. Conclusion： The domestic citalopram hydrobromide tablets are bioequivalence to the imported one.