坎地沙坦酯胶囊在中国健康人体的生物等效性研究  

Bioequivalence of candesartan cilexeticcapsule in Chinese healthy subjects

作　　者：徐素梅[1] 郭韧[2] 李丹[1] 李筱旻[1] 李岱[1] 

机构地区：[1]中南大学湘雅医院国家药物临床试验机构,长沙410008 [2]中南大学湘雅三医院药剂科,长沙410008

出　　处：《中国临床药理学杂志》2017年第6期509-512,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究国产坎地沙坦酯胶囊与进口坎地沙坦酯片在中国健康人体内的生物等效性。方法采用随机开放双交叉试验设计,24例健康男性受试者在空腹状态下单剂量口服国产坎地沙坦酯胶囊(受试药物)和进口坎地沙坦酯片(参比药物)8 mg,以液质联用(LC-MS/MS)法测定血浆中坎地沙坦的浓度。用WinNonlin软件计算药代动力学参数及生物等效性评价。结果受试药物与参比药物的t_(1/2)分别为(9.30±1.70)和(9.80±1.90)h;t_(max)分别为(4.00±0.80)和(4.20±1.00)h;C_(max)分别为(76.98±22.22)和(87.35±34.61)μg·L^(-1);AUC_(0-48h)分别为(826.60±204.10)和(928.00±269.30)μg·h·L^(-1);AUC_(0-∞)分别为(857.10±201.30)和(956.10±270.60)μg·h·L^(-1)。受试药物的相对生物利用度为(114.40±27.30)%。受试药物经对数转换后的药代动力学参数AUC_(0-48h)、AUC_(0-∞)、C_(max)的90%置信区间分别落在参比药物的101.37%~121.80%,101.08%~120.15%,98.59%~119.54%。t_(max)经非参数检验无显著性差异。结论本研究建立的LC-MS/MS法准确快速,灵敏度高,专属性强,适用于坎地沙坦血药浓度测定;国产坎地沙坦酯胶囊与进口坎地沙坦酯片具有生物等效性。Objective Toinvestigate the bioequivalence of domestic candesartan cilexetil capsules and imported candesartan cilexetil tablets in Chinese healthy subjects.Methods This is open,random and two-way crossover clinical trial involved 24 healthy male subjects.A single oral dose 8 mg of domestic candesartan cilexetil capsules（test preparation） and imported candesartan cilexetil tablets（control preparation） was administrated under the condition of fasting.The plasma concentrations of candesartan were determined by LC-MS/MS.The pharmacokinetics parameters were calculated and the bioequivalence of two formulations were evaluated by WinNonlin program.Results The main pharmacokinetic parameters of the test and control preparation were as follows：t1/2（9.30 ± 1.70）,（9.80 ± 1.90） h;tmax（4.00 ± 0.80）,（4.20 ± 1.00）h;Cmax（76.98 ±22.22）,（87.35 ±34.61） μg · L^-1;AUC0-48h（826.60 ±204.10）,（928.00 ±269.30） μg · h · L^-1;AUC0-∞（857.10 ±201.30）,（956.10 ± 270.60） μg · h · L^-1.The relative bioavailability of the test preparation（candesartan cilexetil capsules） was（114.40 ±27.30）%.And 90%confidence limit of test preparation of the logarithmic transformed parameters AUC0-48h,AUC0-∞,Cmax were in 101.37%-121.80%,101.08%-120.15%,98.59%-119.54%compared with reference preparation,respectively.No significant difference was found by nonparametric test of tmax.Conclusion The developed and validated method is rapid,sensitive,selective and reliable for the determination of candesartan in human plasma.The domestic candesartan cilexetil capsules are bioequivalence to the imported candesartan cilexetil tablets.

关 键 词：坎地沙坦酯 药代动力学参数 生物等效性 液质联用法 

分 类 号：R972.4[医药卫生—药品]