摘要
目的:观察国产选择性5-羟色胺再摄取抑制剂氢溴酸西酞普兰片在正常人体内的药物代谢动力学行为,并与进口氢溴酸西酞普兰片进行生物等效性的对比。方法:选择经医院伦理委员会审议通过的健康男性志愿受试者20人。实验前签署知情同意书,受试期间停服任何药物,并禁烟和酒。采用随机交叉设计,口服国产氢溴酸西酞普兰片和进口氢溴酸西酞普兰片剂40mg,(国产氢溴酸西酞普兰片由北京万全药物技术开发有限公司和徐州恩华药业集团有限责任公司共同研发,20mg/片;进口氢溴酸西酞普兰片,商品名希普妙,丹麦灵北药厂,20mg/片)。服药后0.5～132h内间隔取血。血样加入内标盐酸普萘洛尔经预处理后用高效液相色谱测定。计算主要药物代谢动力学参数,并以进口片剂为参比制剂,估算国产氢溴酸西酞普兰片的生物利用度,判断其生物等效性。结果:志愿者1人缺席,1人在第一轮试验服药后1h发生呕吐,且132h的血药浓度为7.1μg/L,0.5h血药浓度为0,吸收和代谢均有影响,故舍去;其余18人进入结果分析。国产氢溴酸西酞普兰片和进口氢溴酸西酞普兰片的血药浓度-时间曲线均符合二房室模型,其血药浓度-时间曲线下面积AUC0-132分别为(1894.6±460.2)μg/(h·L)和(1876.9±398.3)μg/(h·L),差异无显著性(P>0.05);达峰浓度分别为(46.1±9.8)μg/L和(47.7±11.7)μg/L,差异无显著性(P>0.05);半衰期分别为(37.6±10.0)h和(38.8±9.8)h,差异无显著性(P>0.05);达峰时间分别(3.2±1.9)h和(3.2±1.5)h,差异无显著性(P>0.05)。以进口制剂为对照,用血药浓度-时间曲线下面积AUC0-132计算的国产氢溴酸西酞普兰片生物利用度为(100.3±11.7)%。结论:国产氢溴酸西酞普兰片与进口氢溴酸西酞普兰片具有生物等效性。
AIM： To observe the pharmacokinetics of the selective serotonin reuptake inhibitor （SSRI） of domestic citalopram hydrobromide in normal people, and compare its bioequivalence with the import ones,
METHODS： Twenty made healthy volunteers were selected by the Ethics Committee of the hospital after discussion and they all signed the informed consent before study, tbey withdrew any medicine during the study, smoking and drinking were not allowed. Art open randomized crossover design was performed, the volunteers orally took domestic and import citalopram hydrohromide tablets （40 mg）, The domestic eitalopram hydrobromide tablets were researched and developed by Beijing Wanquan Pharmacological Technical Development Co, Ltd together with Xuzhou Enhua Phamacological Group, 20 mg per tablet, and the import citalopram hydrobromide tablets named Cipramil was produeed by Lundbeck Pharmaceutical Factory （Danmark）, 20 mg per tablet. Blood samples were collected periodically at 1.5-132 hours after medication, the plasma was determined by high performance liquid chromatography after treated with inner-labeled propranolole hydrochloride, The pharmaeokinetic parameters were calculated, and the import tablets were taken as controls, the bioavailability was estimated and the hioequivalence was judged.
RESULTS： One volunteer vomited in the first medication, and the drug concentration in blood was 7.1 μg/L at 132 hours and 0 at 0.5 hour, both the absorption and metabolism were affected, so he was excluded; another 1 volunteer withdrew and all the other 18 volunteers were involved in the analysis of results. The concentration-time curves of both domestic and import citalopram hydrobromide tablets were fit to two compartment models with oral absorption. The area under the curve （AUC0-132） had no significant difference [（1 894.6±460.2）, （1 876.9±398.3） μg/L per hour, P 〉 0.05], the peak concentration also had no significant difference [（46.1±9.8）, （47.7±11.7） μg/L, P 〉 0.05], half life was not significantly different [（37.6±10.0）, （38.8±9.8） hours, P 〉 0.05], there was also no significant difference in the peak-reaching time [（3.2±1.9）, （3.2±1.5） hours, P 〉 0.05]. Taken the import tablets as control, the bioavailability of domestic citalopram hydrobromide tablet calculated by concentration-time AUC0-132 was （100.3±11.7）%.
CONCLUSION： The domestic and import citalnpram hydrobromide tablets are bioequivalent.
出处
《中国临床康复》
CSCD
北大核心
2006年第14期111-113,共3页
Chinese Journal of Clinical Rehabilitation
