磷酸瑞格列汀结合缬沙坦在健康志愿者体内的药代动力学分析

Pharmacokinetic analysis of repagliptin phosphate combined with valsartan in healthy volunteers

目的分析健康人口服磷酸瑞格列汀和缬沙坦后体内的药代动力学变化。方法随机选取医院体检的健康志愿者20例进行研究(男女比例1∶1),口服磷酸瑞格列汀片和缬沙坦胶囊,通过液相色谱串联质谱测定受试者血浆中的瑞格列汀、瑞格列汀酸和缬沙坦的药物浓度,同时对药代动力学参数的变化进行分析。结果单独服用磷酸瑞格列汀或与缬沙坦结合服用后,其主要产物磷酸瑞格列汀和磷酸瑞格列汀酸的药代动力学的趋势基本保持一致;此外,与单独服用磷酸瑞格列汀相比,磷酸瑞格列汀与缬沙坦结合服用后,其在Cmax、AUClast、AUCINFobs方面差异无统计学意义(P>0.05);同时,磷酸瑞格列汀和磷酸瑞格列汀酸的Cmax、AUC的90%置信区间介于80%~125%范围内的等效区间内;受试者在服用瑞格列汀和缬沙坦24 h后,其尿液中瑞格列汀和缬沙坦的累积排泄率未发生显著改变。结论健康人群同时服用磷酸瑞格列汀和缬沙坦后,在其体内未发现相互干扰的药代动力学参数变化。

Objective To analyze the pharmacokinetics of healthy people after oral administration of repagliptin phosphate and valsartan.Methods Twenty healthy volunteers from the hospital were randomly selected for study(1∶1 male to female ratio).They were orally administered with repagliptin phosphate tablets and valsartan capsules.The concentration of repagliptin,repagliptin and valsartan in the plasma of the subject was determined by liquid chromatography-tandem mass spectrometry,and the changes in pharmacokinetic parameters were analyzed.Results After taking repagliptin phosphate alone or in combination with valsartan,the main pharmacokinetics of repagliptin phosphate and repagliptin phosphate were basically the same;In addition,compared with rigagliptin phosphate alone,there was no significant difference in Cmax,AUClast,AUCINFobs after taking rigagliptin phosphate in combination with valsartan(P>0.05).After taking rigagliptin phosphate alone or in combination with valsartan,the main products of repagliptin phosphate and repagliptin phosphate,had a consistent trend in pharmacokinetics;Meanwhile,the 90%confidence intervals of Cmax and AUC of repagliptin phosphate and repagliptin phosphate were in the equivalent range of 80%to 125%;The cumulative excretion rates of repagliptin and valsartan in the urine did not change significantly after 24 h of rigagliptin and valsartan.Conclusion After taking repagliptin phosphate and valsartan in healthy people,no changes in the pharmacokinetic parameters of mutual interference were found in the body.