曲美布汀分散片健康人体内的药代动力学及生物等效性研究  

Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy subjects

作　　者：姜红[1] 丁黎[1] 杨劲[2] 黄鑫[1] 刘广余[3] 张正行[1] 

机构地区：[1]中国药科大学药物分析教研室,江苏南京210009 [2]中国药科大学药物代谢研究中心,江苏南京210009 [3]南京医科大学第一附属医院国家药品临床研究基地,江苏南京210029

出　　处：《药学学报》2004年第3期208-211,共4页Acta Pharmaceutica Sinica

摘　　要：目的　建立人血浆中曲美布汀的HPLC ESI MS测定法 ,研究曲美布汀在正常人体内的药代动力学行为 ,评价其两种制剂的生物等效性。方法　血浆样品经碱化以环己烷提取 ,进行HPLC ESI MS分析 ,内标为西布曲明 ,检测离子为m z 388(曲美布汀 )、m z 2 80 (内标 ) ,裂解电压为 5 0V。 2 0名健康志愿者交叉口服供试片和参比片 ,剂量均为 10 0mg。结果　受试制剂及参比制剂的曲美布汀消除半衰期分别为 (9 2± 2 3)h和 (9 2± 2 8)h ,达峰时间分别为 (0 9± 0 4 )h和 (1 0± 0 3)h ,峰浓度分别为 (41± 2 0 ) μg·L- 1 和 (40± 2 0 ) μg·L- 1 。以AUC0 - 2 4h 计算的受试制剂的相对生物利用度为 (97± 13) %。结论　本法灵敏、准确、简便。统计学结果表明两种制剂生物等效。Aim To develop an HPLC-ESI-MS assay for determination of trimebutine in human plasma and to investigate the pharmacokinetics and bioequivalence of two trimebutine tablets in human. Methods After being made alkaline with saturated sodium bicarbonate, plasma was extracted by cyclohexane and separated by HPLC on a reversed-phase C 18 column with a mobile phase of 10 mmol·L -1 ammonium acetate buffer solution (pH 3.5)-methanol (18∶82). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 388 for trimebutine and m/z 280 for the internal standard (sibutramine, IS). The fragmentor voltage was 50 V. A randomized cross-over design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer. Results Calibration curve was linear over the range of 0.3-150 μg·L -1 . The main pharmacokinetic parameters of T 1/2 , T max and C max were (9.2±2.8) h, (1.0±0.3) h and (40±20) μg·L -1 for the reference tablet; (9.2±2.3) h, (0.9±0.4) h and (41±20) μg·L -1 for the test tablet. The relative bioavalability of the test tablet was (97±13)%. The results of variance analysis and two one-sided t -test showed that there was no significant difference between the two formulations in the AUC and C max . Conclusion The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

关 键 词：曲美布汀分散片 人体健康 药代动力学 生物等效性 胃功能调节剂 

分 类 号：R975.1[医药卫生—药品] R969.1[医药卫生—药学]