单剂量与多剂量口服单硝酸异山梨酯缓释胶囊的人体生物等效性研究  

Single-dose and multi-dose bioavailability of isosorbide-5-mononitrate sustbilityained release capsules in Chinese healthy subjects

作　　者：淳泽利 刘文芳[2] 林阳[2] 杨克旭[2] 赵桂平[2] 鲁春艳[2] 谭莉[2] 张颖超[2] 吴伟[2] 所伟[2] 李静[2] 周子杰[2] 杜海燕[2] 仇琪[2] 赵颖[1] 刘有平[1] 

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]首都医科大学附属北京安贞医院临床药理中心,北京100029

出　　处：《中国临床药理学杂志》2015年第17期1727-1731,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种单硝酸异山梨酯缓释胶囊在中国健康男性体内的生物等效性。方法单剂量给药24名、多剂量给药26名健康男性受试者随机分为2组,根据交叉试验设计方案,单剂量给予50 mg和多剂量给予50 mg（1天1次,连续6 d）两种单硝酸异山梨酯缓释胶囊,用液相色谱串联质谱法测定其血药浓度,并计算药代动力学参数。结果单剂量给药受试药物和参比药物的主要药代动力学参数：Cmax为（554.18±117.84）和（526.29±91.58）μg·L-1;AUC0-t为（7834.21±1227.70）和（7658.86±927.74）h·μg·L-1,以Cmax和AUC0-t计算,受试药物90%的置信限分别为参比药物的99.82%~113.03%和99.13%~106.43%。多剂量给药受试药物和参比药物的主要药代动力学参数：Cmax为（612.96±171.32）和（527.12±114.36）μg·L-1;AUC0-t为（8408.71±1321.91）和（7781.88±1325.12）h·μg·L-1,以Cmax和AUC0-t计算,受试药物90%的置信限分别为参比药物的108.44%~122.17%和105.35%~111.57%。单剂量给药、多剂量给药受试药物Cmax90%的置信限均在参比药物的70%~143%;AUC0-t的90%置信限均在参比药物的80%~125%。结论受试药物和参比药物具有生物等效性。Objective To compare the pharmacokinetic profiles between a new generic and a branded reference formulation of isosorbide- 5-mononitrate sustained release capsules,and to assess the bioequivalence of the two products in healthy Chinese male subjects. Methods Fifty subjects participated in the open- label, randomized- sequence,2- way crossover study. Twenty- four subjects and 26 subjects were randomly assigned in a 1： 1 ratio to receive single dose（ 50 mg） or multiple dose（ 50 mg,qd,6 days） of the test or reference formulation,followed by a one- week washout period and administration of the alternate formulation, respectively. Serial blood samples were collected, and isosorbide- 5- mononitrate concentration in plasma was determined by LC- MS / MS. The relative bioavailability and related parameters of pharmacokinetics were calculated. Results The pharmacokinetic parameters of test formulation and the reference formulation after a single dose were as follows： Cmaxwere（ 554. 18 ± 117. 84） and（ 526. 29 ± 91. 58） μg·L- 1; AUC0- twere（ 7834. 21 ± 1227. 70） and（ 7658. 86 ±927. 74） h·μg·L- 1,respectively. The 90% confidential interval of Cmaxand AUC0- tof test formulation were 99. 82%- 113. 03% and 99. 13%- 106. 43% of reference formulation,respectively. The pharmacokinetic parameters of test formulation and the reference formulation after multiple doses were as follows： Cmaxwere（ 612. 96 ± 171. 32）and（ 527. 12 ± 114. 36） μg · L- 1; AUC0- twere（ 8408. 71 ± 1321. 91） and（ 7781. 88 ± 1325. 12） h · μg · L- 1,respectively. The 90% confidential interval of Cmaxand AUC0- tof test formulation were 108. 44%- 122. 17% and105. 35%- 111. 57% of reference formulation,respectively. The 90% confidence interval of Cmaxand AUC0- tof isosorbide- 5- mononitrate for the test formulation after single and multiple oral doses were fall within 70%- 143% and80%- 125% of reference formulation. Conclusion The test formulation was considered bioequivalent to the reference formulation.

关 键 词：单硝酸异山梨酯 生物等效性 药代动力学 液相色谱串联质谱法 

分 类 号：R972[医药卫生—药品] R969[医药卫生—药学]