匹伐他汀钙分散片在中国健康受试者的生物等效性研究  

Bioequivalence study of pitavastatin calcium dispersible tablets in healthy Chinese volunteers

作　　者：张薇 潘春苗 王小丹 胡殷[2] 邵蓉[1] 江波[1] ZHANG Wei;PAN Chun-miao;WAN Xiao-dan;HU Yin;SHAO Rong;JIANG Bo(Center of Clinical Pharmacology,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,Zhejiang Province,China;Nursing Department,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,Zhejiang Province,China;Zhejiang Jingxin Pharmaceutical Co.,Ltd,Xinchang 312500,ZhejianggProvince,China)

机构地区：[1]浙江大学医学院附属第二医院临床药理中心,浙江杭州310009 [2]浙江大学医学院附属第二医院护理部,浙江杭州310009 [3]浙江京新药业股份有限公司,浙江新昌312500

出　　处：《中国临床药理学杂志》2024年第10期1497-1501,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家卫生健康委重大新药创制国家科技重大专项基金资助项目(2020ZX09201022)。

摘　　要：目的比较匹伐他汀钙分散片在中国健康人体内的生物利用度和生物等效性。方法用随机、开放、自身交叉、单次给药试验设计,分别在空腹和餐后条件下,健康受试者随机交叉单剂量口服匹伐他汀钙受试制剂或参比制剂2 mg,用高效液相色谱串联质谱法(HPLC-MS/MS)测定受试者服药前后不同时间点血浆内药物浓度,用WinNonlin 7.0软件计算主要药代动力学参数,并评价2种制剂的生物等效性。结果受试者空腹服用匹伐他汀钙受试制剂和参比制剂的C_(max)分别为(47.79±23.99)和(46.03±21.82)ng·L^(-1),AUC_(0-t)分别为(96.56±42.64)和(97.96±35.40)ng·h·L^(-1),AUC_(0-∞)分别为(102.09±43.01)和(103.46±35.62)ng·h·L^(-1)。受试者空腹服用匹伐他汀钙受试制剂和参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比的90%置信区间分别为96.28%~111.16%、94.46%~101.19%和94.77%~101.31%。受试者空腹服用匹伐他汀钙受试制剂和参比制剂的C_(max)分别为(27.32±10.68)和(28.58±11.39)ng·L^(-1),AUC_(0-t)分别为(82.76±27.58)和(84.06±29.12)ng·h·L^(-1),AUC_(0-∞)分别为(87.88±26.93)和(89.29±29.18)ng·h·L^(-1)。受试者餐后服用匹伐他汀钙受试制剂和参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比的90%置信区间分别为87.39%~102.10%、94.62%~101.34%和94.88%~101.47%,均在80.00%~125.00%的生物等效性范围内。结论2种匹伐他汀钙分散片在中国健康成人受试者中具有生物等效性,且安全性良好。Objective To compare thebioavailability and bioequivalence of pivastatin calcium dispersive tablets in healthy Chinese subjects.Methods A single dose of pitavastatin calcium(2 mg)was orally administered to the test preparation or reference preparation under fastingandpostprandialconditions,rrespectively.Theplasma concentrations of pitavastatin calcium were measured at different time points before and after administration by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The bioequivalence of the two formulations was evaluated.Results Subjects received pitavastatin calcium test preparation and reference preparation in fasting condition,the C_(max) were(47.79±23.99)and(46.03±21.82)ng·L^(-1);AUC_(0-t)were(96.56±42.64)and(97.96±35.40)ng·h·L^(-1);AUC_(0-∞)were(102.09±43.01)and(103.46±35.62)ng·h·L^(-1),respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t)and AUC_(0-∞)of pitavastin-calcium test formulation and reference formulation were 96.28%-111.16%,94.46%-101.19%and 94.77%-101.31%,respectively.Subjects received pitavastatin calcium test preparation and reference preparation in fasting condition,the C_(max) were(27.32±10.68)and(28.58±11.39)ng·L^(-1);AUC_(0-t)were(82.76±27.58)and(84.06±29.12)ng·h·L^(-1);AUC_(0-∞)were(87.88±26.93)and(89.29±29.18)ng·h·L^(-1),respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t)and AUC_(0-∞)of the test formulation and the reference formulation of pitavastatin calcium were 87.39%-102.10%,94.62%-101.34%and 94.88%-101.47%,respectively.All of them were within the bioequivalence range of 80.00%to 125.00%.Conclusion Two pivastatin calcium dispersion tablets were bioequivalent and safe in healthy Chinese adult subjects.

关 键 词：匹伐他汀钙分散片 高效液相色谱串联质谱法 药代动力学 生物等效性 

分 类 号：R972[医药卫生—药品]