单剂量口服复方缬沙坦分散片的人体药动学研究

Pharmacokinetics of Valsartan and Hydrochlorothiazide in Healthy Volunteers after Single Administration of Its Compound Dispersible Tablets

目的:研究单剂量口服复方缬沙坦分散片的药动学特征。方法:采用高效液相色谱法测定人血浆中氢氯噻嗪与缬沙坦的浓度,由DAS软件计算药动学参数。结果:氢氯噻嗪低、中、高剂量主要药动学参数t1/2分别为(12.56±3.66)、(11.47±5.47)、(11.20±5.03)h,Cmax分别为(72.00±19.68)、(169.96±52.17)、(203.66±61.41)ng.mL-1,AUC0～48分别为(592.87±179.44)、(1155.45±252.03)、(1410.99±331.82)ng.h.mL-1,AUC0～∞分别为(779.76±201.42)、(1246.89±307.03)、(1482.14±332.20)ng.h.mL-1;缬沙坦低、中、高剂量主要药动学参数t1/2分别为(7.29±3.10)、(8.56±2.22)、(8.62±2.86)h,Cmax分别为(2.12±0.65)、(6.76±2.08)、(6.71±2.59)ng.mL-1,AUC0～48分别为(18.16±4.52)、(41.77±10.86)、(51.77±27.45)ng.h.mL-1,AUC0～∞分别为(19.07±5.56)、(42.60±11.18)、(53.49±26.93)ng.h.mL-1。结论:复方缬沙坦分散片体内为线性动力学过程,缬沙坦与氢氯噻嗪合用时,氢氯噻嗪与缬沙坦的药动学无相互影响。

OBJECTIVE： To study the pharmacokinetics of hydrochlorothiazide and valsartan in healthy volunteers after single administration of its compound dispersible tablets. METHODS： Plasma concentrations of hydrochlorothiazide and valsartan were determined by HPLC and their pharmacokinetic parameters were calculated with DAS software. RESULTS： The pharmacokinetic parameters of hydrochlorothiazide at low, medium and high doses were as follows： t 1/2 were （12.56±3.66）, （11.47± 5.47） and （11.20± 5.03） h, respectively; Cmax were （72.00± 19.68）, （169.96± 52.17） and （203.66± 61.41）ng · mL^- 1, respectively; AUC0-48 were （592.87± 179.44）, （1 155.45±252.03） and （1 410.99±331.82） ng·h·mL^-1. respectively; AUC0-∞ were （779.76±201.42）, （1 246.89±307.03） and （1 482.14±332.20） ng·h·mL^-1, respectively. The pharmacokinetic parameters of valsartan at low, medium and high doses were as follows： t 1/ 2 were （7.29± 3.10）, （8.56 ± 2.22） and （8.62±2.86）h, respectively; Cmax were （2.12±0.65）, （6.76±2.08） and （6.71±2.59）ng · mL^-1, respectively; AUC0-48 were （18.16±4.52）, （41.77±10.86） and （51.77±27.45） ng·h·mL^-1 respectively; AUC0-∞ were （19.07± 5.56）, （42.60 ± 11.18） and （53.49 ± 26.93） ng·h·mL^-1 respectively. CONCLUSION ： The pharmacokinetics for compound valsartan dispersible tablet fitted linear kinetics process. There is no interaction in pharmacokinetics between hydrochlorothiazide and valsartan when they used in combination.