目的 研究鹽酸文拉法辛緩釋片在Beagle犬體內(nèi)的藥動(dòng)學(xué)和生物等效性。方法 8條健康Beagle犬隨機(jī)分成2組，采用雙周期、雙交叉、單劑量分別ig鹽酸文拉法辛緩釋片受試制劑或參比制劑75 mg，清洗期為1周；建立血漿中鹽酸文拉法辛液相色譜-質(zhì)譜聯(lián)用（LC-MS/MS）檢測(cè)方法，進(jìn)行方法精密度、準(zhǔn)確度、提取回收率、基質(zhì)效應(yīng)、穩(wěn)定性方法學(xué)驗(yàn)證；測(cè)定給藥前（0 h）及給藥后2、3、4、5、6、8、10、12、14、16、24、36、48、72 h血漿中鹽酸文拉法辛血藥濃度，運(yùn)用DAS 2.1.1軟件計(jì)算其藥動(dòng)學(xué)參數(shù)，并評(píng)價(jià)其生物等效性。結(jié)果 LC-MS/MS方法學(xué)經(jīng)驗(yàn)證符合檢測(cè)要求，受試制劑和參比制劑主要藥動(dòng)學(xué)參數(shù)分別如下：T_1/2分別為（7.16±2.34）和（6.95±1.57） h、Cmax分別為（522.89±201.12）和（515.22±159.29）ng/mL、T_max分別為（10.38±1.69）和（10.50±2.07）h、AUC_0-t分別為（8 398.64±3332.86）和（8 050.71±2103.15）ng·h/mL、AUC_0-∞分別為（8 701.60±3303.29）和（8 450.01±2273.45）ng·h/mL；以參比制劑為參考，受試制劑AUC_0-∞相對(duì)生物利用度為（101.0±13.1）%。結(jié)論 鹽酸文拉法辛緩釋片受試制劑與參比制劑在Beagle犬體內(nèi)具有生物等效性。

Objective To investigate the pharmacokinetic profiles and bioequivalence of Venlafaxine hydrochloride sustained release tablets.Methods Eight healthy Beagle dogs were ig given Venlafaxine hydrochloride sustained-release tablets or reference tablets of 75 mg in two-cycle, double-crossover and single-dose respectively. A method for the determination of Venlafaxine hydrochloride in plasma by LC-MS/MS was established. The method was validated for precision, accuracy, recovery, matrix effect and stability. The blood concentration of Venlafaxine hydrochloride in plasma was determined before (0 h) and 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72 h after administration. The pharmacokinetic parameters were calculated by DAS 2.1.1 and its bioequivalence was evaluated. Results LC-MS/MS methodologies were verified to meet the detection requirements. The main pharmacokinetic parameters of Venlafaxine test and reference preparations were as follows:T_1/2, (7.16±2.34) and (6.95±1.57) h; Cmax, (522.89±201.12) and (515.22±159.29) ng/mL; T_max, (10.38±1.69) and (10.50±2.07) h; AUC0-t, (8 398.64±3 332.86) and (8 050.71±2 103.15) ng·h/mL;AUC_0-∞,(8 701.60±3 303.29) and (8 450.01±2 273.45) ng·h/mL, respectively. The relative bioavailability of Venlafaxinewas (101.0±13.1)%。Conclusion Venlafaxine hydrochloride sustained-release tablets have bioequivalence with reference tablets in Beagle dogs.

國家重大專項(xiàng)新藥創(chuàng)制（2017ZX09201003-006）