磷酸瑞格列汀和缬沙坦在健康人体的药代动力学相互作用研究  

Pharmacokinetic interactions between retagliptin phosphate and valsartan in healthy subjects

作　　者：雍小兰[1] 冯仕银[1] 李楠[1] 黄娟[1] 王蓝天[1] 康辉[1] 

机构地区：[1]成都军区总医院临床药学科

出　　处：《中国临床药理学与治疗学》2016年第6期661-666,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的：研究磷酸瑞格列汀和缬沙坦口服后在健康人体的药代动力学相互作用及影响。方法：采用随机、二阶段交叉方法,选择健康志愿者16例,男女各半,口服磷酸瑞格列汀片和缬沙坦胶囊。采用液相色谱串联质谱分别测定血浆中的缬沙坦、瑞格列汀和瑞格列汀酸的药物浓度。分析tmax、Cmax、AUClast、AUCinf、90%CI等药代动力学参数变化。结果：与单用比较,瑞格列汀与缬沙坦合用后,瑞格列汀的Cmax升高约4.03%,其AUC和主要活性代谢物瑞格列汀酸的AUC和Cmax的90%置信区间在80%～125%的等效性区间内;缬沙坦的Cmax降低了11.58%,AUClast降低了约4.73%,与单独用药相比,AUC比值的90%置信区间均在80%～125%的等效性区间内。瑞格列汀与缬沙坦合用后24 h尿液中瑞格列汀和缬沙坦的累积排泄率的改变没有统计学意义（P〈0.05）。二药代谢途径和代谢程度无明显改变。结论：磷酸瑞格列汀和缬沙坦同服后在健康人体内无明显药代动力学相互作用。AIM： To investigate pharmacokinet- ic interactions between retagliptin phosphate and valsartan in healthy subjects after oral administration. METHODS： Randomized to receive open, cross-over trial, 16 healthy subjects were administered with retagliptin phosphate tablets and valsartan capsule. LC-MS/MS was used to examine plasma concentration of retagliptin, retagliptin acid, valsartan and other parameters including tmax max, C AUClast AUCinf and 90% CI. RESULTS： As compared with administration alone, Cmax ofretagliptin increased by around 4.03% after coadministration with valsartan. 90% confidence interval of the AUC of retagliptin and retagliptin acid and the Cmax of retagliptin acid was within the equivalent interval of 80% - 125%. Cmax and AUClast of valsartan were reduced by 11.58% and 4.73%, respectively. Compared with medication alone, 90% confidence interval of the ratio of AUC of valsartan co-administered with reta-gliptin was within the equivalent interval of 80% - 125%. There were insignificant changes in cumulative excretion rateofretagliptin and valsartan in 24 h urine after co-administration （P 〈 0.05 ）, and their metabolic pathways and levels had no significant change. CONCLUSION： There are no significant pharmacokinetic interactions between retagliptin and valsartan in healthy subjectsfollowing their co-administration.

关 键 词：磷酸瑞格列汀 缬沙坦 液相色谱串联质谱 药代动力学 

分 类 号：R969.1[医药卫生—药理学]