目的 在健康受試者中空腹及餐后情況下評價纈沙坦片的吸收速度和吸收程度，評價受試制劑和參比制劑是否具有生物等效性。方法 采用開放、單劑量、隨機(jī)、3周期、部分重復(fù)交叉設(shè)計的生物等效性研究。每周期口服受試制劑或參比制劑40 mg。應(yīng)用液相色譜-串聯(lián)質(zhì)譜（LC-MS/MS）方法測定血漿中纈沙坦?jié)舛?，使用WinNonlin^® 6.4軟件，計算藥動學(xué)參數(shù)，評價兩種制劑的生物等效性。結(jié)果 空腹組受試制劑與參比制劑藥時曲線下面積（AUC_0～t）和AUC_0～∞的幾何均數(shù)比值分別為100.39%和100.35%，90%置信區(qū)間（90% CI）分別為91.91%～109.67%和92.11～109.32%，完全落入80.00%～125.00%內(nèi)。達(dá)峰濃度（C_max）幾何均值比值為97.61%，落在80.00%～125.00%內(nèi)。餐后組受試制劑與參比制劑C_max、AUC_0～t和AUC_0～∞的幾何均數(shù)比值分別為107.85%、105.03%和105.06%，90% CI分別為97.81%～118.92%、99.27%～111.12%和99.42%～111.02%，完全落入80.00%～125.00%內(nèi)。結(jié)論 纈沙坦片受試制劑和參比制劑在空腹和餐后狀態(tài)下均具有生物等效性。

Objective The rate and degree of absorption of Valsartan Tablets and DIOVAN were evaluated on fasting and postprandial conditions in healthy male and female subjects to evaluate the bioequivalence between the two preparations. Methods An open, single-dose, randomized, three-cycle, partially replicated crossover design was used to study bioequivalence. Oral administration of test preparation or reference preparation 40 mg percycle. Oral administration of test preparation or reference preparation 40 mg per cycle. Plasma concentration of valsartan was determined by liquid chromatographer-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated by WinNonlin^® 6.4 software to evaluate the bioequivalence of the two preparations. Results The main pharmacokinetic parameters of fasting group were as follows:The geometric mean ratios of AUC_0-t and AUC_0-∞ between test preparation or reference preparation were 100.39% and 100.35%, respectively. The 90% confidence intervals were 91.91%-109.67% and 92.11-109.32%, respectively. It's totally in the 80.00%-125.00% range. The point estimate of the geometric mean ratio of C_max is 97.61%, which falls in the range of 80.00%-125.00%. The main pharmacokinetic parameters of the postprandial group are as follows:The geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ between test preparation or reference preparation were 107.85%, 105.03% and 105.06%, respectively. The 90% confidence intervals are 97.81%-118.92%, 99.27%-111.12% and 99.42%-111.02%, respectively, which completely fall into the range of 80.00%- 125.00%. Conclusion The test preparation of Valsartan Tablets were bioequivalent to reference preparation in fasting and postprandial states.

R969.1

江蘇省新藥研究與臨床藥學(xué)重點實驗室開放研究課題（KFKT-2110）