海曲泊帕对瑞舒伐他汀在健康受试者中的药代动力学影响  

Effects of hetrombopag on rosuvastatin pharmacokinetics in Chinese healthy subjects

作　　者：瞿文君 张吉刚[1] 张铭健 曹佩 赫慧琛 丁雪鹰[1] QU Wen-jun;ZHANG Ji-gang;ZHANG Ming-jian;CAO Pei;HE Hui-chen;DING Xue-ying(Clinical Research Center,Shanghai First People’s Hospital Affiliated to Shanghai Jiaotong University,Shanghai 200080,China)

机构地区：[1]上海交通大学附属第一人民医院临床研究中心,上海200080

出　　处：《中国临床药理学杂志》2022年第22期2751-2755,共5页The Chinese Journal of Clinical Pharmacology

基　　金：市级医院医企协同临床试验管理基金资助项目(20CR4001A)。

摘　　要：目的评估一类新药乳腺癌耐药蛋白(BCRP)抑制药海曲泊帕对BCRP底物瑞舒伐他汀在健康受试者中的药代动力学影响。方法入选14名健康受试者进行瑞舒伐他汀与海曲泊帕的联合给药,分别在第1天和第11天空腹给予瑞舒伐他汀10 mg,同时在第6~11天早上给予海曲泊帕7.5 mg。在第1天瑞舒伐他汀钙片给药前后,在第11天联合用药前后不同时间点采集静脉血,用高效液相色谱串联质谱测定血浆中瑞舒伐他汀的浓度。结果联合使用海曲泊帕后血浆中瑞舒伐他汀的C_(max)为(14.64±6.12)ng·mL^(-1)、AUC_(0-t)为(144.06±61.80)h·ng·mL^(-1)、AUC_(0-∞)为(148.20±62.54)h·ng·mL^(-1),与单用瑞舒伐他汀相比,C_(max)、AUC_(0-t)、AUC_(0-∞)几何最小二乘均值比值及其90%置信区间分别为112.87%(101.95%~124.96%)、110.28%(103.93%~117.01%)、110.28%(103.67%~117.32%),均落在80.00%~125.00%范围之内。结论在健康受试者中,海曲泊帕对瑞舒伐他汀的药代动力学暴露量没有影响。Objective To evaluate the pharmacokinetic effects of hetrombopag on the pharmacokinetics of rosuvastatin,a substrate for breast cancer resistance protein,in healthy subjects.Methods Fourteen healthy subjects were enrolled for the combined administration of rosuvastatin and hetrombopag.Fourteen subjects were given rosuvastatin 10 mg on the 1^(st) day and 11^(th) day.Hetrapopag 7.5 mg was given every morning from 6^(th) day to 11^(th) day.Before and after administration of rosuvastatin calcium tablets on 1^(st) day and 11^(th) day,the plasma samples were collected for the detection of drug concentrations by LC-MS/MS.Results After oral administration of rosuvastatin and hetrombopag,the main pharmacokinetic parameters were calculated and listed as follows:C_(max) were(14.64±6.12)ng·mL^(-1);AUC_(0-t) were(144.06±61.8)h·ng·mL^(-1);AUC_(0-∞)were(148.20±62.54)h·ng·mL^(-1).Compared with the single drug,the geometric least squares mean ratio of C_(max),AUC_(0-t),AUC_(0-∞)of rosuvastatin in plasma after the combination drug(rosuvastatin+hetrombopag)and its 90%confidence interval were 112.87%(101.95%-124.96%),110.28%(103.93%-117.01%),110.28%(103.67%-117.32%).The geometric mean ratios all fell within the range of 80.00%-125.00%.Conclusion In Chinese healthy subjects,hetrombopag has no effect on the pharmacokinetics exposure of rosuvastatin.

关 键 词：瑞舒伐他汀 海曲泊帕 乳腺癌耐药蛋白抑制药 药物相互作用 

分 类 号：R97[医药卫生—药品]