目的 研究腦心通膠囊對(duì)纈沙坦在大鼠體內(nèi)藥動(dòng)學(xué)的影響。方法 建立液相色譜-串聯(lián)質(zhì)譜（LC-MS/MS）法檢測(cè)纈沙坦血藥濃度，并進(jìn)行專屬性考察、回收率試驗(yàn)、基質(zhì)效應(yīng)、穩(wěn)定性試驗(yàn)等方法學(xué)驗(yàn)證；24只SD雄性大鼠，隨機(jī)均分為3組，每組8只，分別為纈沙坦組（A組），纈沙坦和腦心通膠囊單次給藥組（B組），腦心通膠囊給藥7 d后，第8天ig給予纈沙坦和腦心通膠囊組（C組），于給藥前及給藥后不同時(shí)間點(diǎn)由大鼠眼眶靜脈叢采血，采用液相色譜-串聯(lián)質(zhì)譜（LC-MS/MS）法測(cè)定血漿中纈沙坦的質(zhì)量濃度，DAS2.0軟件統(tǒng)計(jì)分析，得到纈沙坦的藥動(dòng)學(xué)參數(shù)。結(jié)果 成功建立LC-MS/MS法檢測(cè)纈沙坦血藥濃度方法，方法學(xué)驗(yàn)證符合藥動(dòng)學(xué)相關(guān)規(guī)范要求。口服纈沙坦在大鼠體內(nèi)的藥動(dòng)學(xué)屬于一室模型。B組C_max明顯低于A組，但差異無統(tǒng)計(jì)學(xué)差異；B組t_1/2顯著高于A組（P<0.05）；C組t_max、t_1/2、AUC_0-tn、AUC_0-∞均顯著高于A組（P<0.05、0.01），K_e顯著低于A組（P<0.05）；C組AUC_0-tn、AUC_0-∞顯著高于B組（P<0.05）。結(jié)論 大鼠經(jīng)連續(xù)ig給藥腦心通膠囊后，可顯著延緩纈沙坦在大鼠體內(nèi)的達(dá)峰時(shí)間，并使纈沙坦在大鼠體內(nèi)的生物利用度升高。

Objective To study the effect of Naoxintong Capsules on pharmacokinetics of valsartan in rats. Methods 24 SD rats were randomly divided into three groups:valsartan group (group A), valsartan group (group B) and Naoxintong Capsules group (group B), each group had 8 rats. On the 8th day, valsartan and Naoxintong Capsules were given by gavage (group C). Plasma samples were collected at different times after the drug administrationfrom the orbital veins of the rats. The concentrations of valsartan in plasma were determined by LC-MS/MS, and the pharmacokinetic parameters of valsartan were obtained in rats by the statistical analysis of DAS 2.0 Software. Results Combined with the valsartan single administration group (group C), t_max, t_1/2, and AUC were significantly increased (P<0.05 or P<0.01), and Ke was significant decreased (P<0.05) in the Naoxintong and valsartan combined administration group. Conclusion The rats significantly delayed the peak time of valsartan, and the bioavailability of valsartan in rats after continuous administration of Naoxintong was increased. It is instructive to study the combined use of valsartan and Naoxintong capsule.

R969.1

國(guó)家自然科學(xué)基金資助項(xiàng)目（81673824）