波生坦片生物等效性研究  

Study on the Bioequivalence of Bosentan Tablets

作　　者：李梦瑶 张婷[1,2] 田杰 姜雅琦 甘方良 王定淼[1] LI Meng-yao;ZHANG Ting;WANG Ding-miao(School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部药学院,湖北咸宁437100 [2]湖北科技学院附属第一医院临床药理机构办公室

出　　处：《湖北科技学院学报（医学版）》2024年第3期221-225,共5页Journal of Hubei University of Science and Technology(Medical Sciences)

摘　　要：目的研究单次空腹、餐后口服波生坦片受试制剂和参比制剂,评价其在中国男性健康受试者中生物等效性。方法采用单中心、随机、开放、单剂量、两制剂、两序列、空腹四周期、餐后两周期交叉设计,选取56例中国健康男性受试者,其中32例参与空腹试验,24例参与餐后试验,单剂量口服波生坦参比制剂或受试制剂125mg。采用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定血浆中波生坦的浓度,采用WinNonlin8.2软件,计算波生坦药代动力学参数,评价两制剂生物等效性。结果空腹试验,波生坦受试制剂和参比制剂主要药动学参数C_(max)、AUC_(0-t)和AUC_(0-∞)分别为(2343.847±1312.224)和(2066.138±1176.744)ng/mL、(11978.6±5643.0)和(10758.8±4878.6)h·ng/mL、(12529.1±5675.0)和(11171.1±4916.5)h·ng/mL;餐后试验受试制剂和参比制剂的波生坦C max、AUC_(0-t)、AUC_(0-∞)分别为(4134.797±1225.003)和(3903.548±975.244)ng/mL、(19704.3±4626.6)和(19020.1±4139.8)h·ng/mL、(19886.0±4640.7)和(19193.1±4158.2)h·ng/mL。空腹和餐后受试制剂与参比制剂C max、AUC_(0-t)和AUC_(0-∞)最小二乘几何均值比的90%置信区间(CI)均落在80.00%~125.00%判定范围内。结论波生坦在空腹和餐后状态下,两制剂在吸收速度和吸收程度上生物等效。Objective To evaluate the bioequivalence of Bosentan tablets and its reference preparations in healthy Chinese male subjects by a single fasting and postprandial-oral administration.Methods Fifty-six Chinese healthy male subjects were selected in a single-center,randomized,open-label,single-dose,two-preparation,two-sequence,four-cycle fasting and two-cycle postprandial crossover design,of which 32 participated in the fasting test and 24 participated in the postprandial test.A single dose of Bosentan reference preparation or test preparation 125 mg was administered orally.The concentration of Bosentan in plasma was determined by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The pharmacokinetic parameters were calculated by using WinNonlin8.2 software to evaluate the bioequivalence of the two preparations.Results In the fasting test,the main pharmacokinetic parameters of Bosentan test and reference preparations were as follows:C_(max)、AUC_(0-t)and AUC_(0-∞)were(2343.847±1312.224)and(2066.138±1176.744)ng/mL,(11978.6±5643.0)and(10758.8±4878.6)h·ng/mL,(12529.1±5675.0)and(11171.1±4916.5)h·ng/mL,respectively.After the meal,the C_(max)、AUC_(0-t)and AUC_(0-∞)of Bosentan test and reference preparations were(4134.797±1225.003)and(3903.548±975.244)ng/mL,(19704.3±4626.6)and(19020.1±4139.8)h·ng/mL,(19886.0±4640.7)and(19193.1±4158.2)h·ng/mL,respectively.The 90%confidence intervals(CI)of C_(max)、AUC_(0-t)and AUC_(0-∞)least-square geometric mean ratio of fasting and postmeal test preparations and reference preparations all fell within the judgment range of 80.00%~125.00%.Conclusion Under fasting and postprandial conditions,the two formulations of bosentan are bioequivalent in terms of absorption rate and degree of absorption.

关 键 词：波生坦片 生物等效性 药动学 超高效液相色谱-串联质谱法 

分 类 号：R917[医药卫生—药物分析学]