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目的:研究大豆异黄酮对盐酸雷洛昔芬在大鼠体内的药动学,并观察大豆异黄酮对盐酸雷洛昔芬药动学参数以及相对生物利用度Frel参数的影响。方法:取SD雌性大鼠8只(390±10)g,随机平均分为两组,对照组为盐酸雷洛昔芬片(RH)组,实验组为大豆异黄酮盐酸雷洛昔芬片(RH-SIF)组,按剂量10.7 mg/kg灌胃给药,分别于0.5、0.75、1、2、4、6、8、12、24、48、72、96、144、192 h取血,处理样品后,以RH为对照品,采用HPLC法测定两组血浆样品中的药物浓度并拟合药时曲线,得出药物动力学参数。采用AIC判别法确定两组制剂在大鼠体内的血药分布所符合的房室模型,并通过AUCT.DR/(AUCR.DT)计算得到RH-SIF片相对生物利用度Frel。结果:①以盐酸雷洛昔芬(RH)为检测指标,给药后两组大鼠体内的主要药动学参数分别为:实验组:Ka为(0.67±0.22)/h,Ke为(0.01±0.00)/h,Tmax为(2.13±0.12)h,Cmax为(0.78±0.02)μg/ml,AUC为(74.64±8.62)μg.h/ml;对照组:Ka为(0.27±0.02)/h,Ke为(0.01±0.00)/h,Tmax为(4.36±1.05)h,Cmax为(0.48±0.13)μg/ml,AUC为(62.73±5.53)μg.h/ml。②与市售的RH片相比,大鼠服用RH-SIF片后,达峰时间明显缩短,达峰浓度明显升高(P<0.05),且两制剂的药时曲线下面积AUC有显著差异(P<0.01)。③相对生物利用度Frel,ie:AUCT.DR/(AUCR.DT)=165.68%。结论:两组制剂在大鼠体内均符合权重为1/C2的单室模型分布,且大豆异黄酮盐酸雷洛昔芬片能明显提高雷洛昔芬的相对生物利用度。
OBJECTIVE: To study the pharmacokinetics of raloxifene hydrochloride in rat by isoflavone, and to observe the effect of soy isoflavone on the pharmacokinetics parameters and the relative bioavailability Frel parameters of raloxifene hydrochloride. Methods: Eight female SD rats (390 ± 10 g) were randomly divided into two groups. The control group was raloxifene hydrochloride (RH) group. The experimental group was soy isoflavone raloxifene hydrochloride tablets RH-SIF group). The mice were orally administered with a dose of 10.7 mg / kg and blood was taken at 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, After the samples were treated, the pharmacokinetic parameters of the two groups of plasma samples were determined by HPLC with RH as the reference substance and the drug concentration curve was fitted by HPLC. The AIC discriminant method was used to determine the atrioventricular model of the two groups of preparations in rats and the relative bioavailability of the RH-SIF tablets was calculated by AUCT.DR / (AUCR.DT). Results: ① The main pharmacokinetic parameters of Raloxifene Hydrochloride (RH) in the two groups were as follows: Ka = 0.67 ± 0.22 / Ke, Ke = 0.01 (0.78 ± 0.02) μg / ml, and the AUC was (74.64 ± 8.62) μg.h / ml in the control group; h, Ke was (0.01 ± 0.00) / h, Tmax was (4.36 ± 1.05) h, Cmax was (0.48 ± 0.13) μg / ml and AUC was (62.73 ± 5.53) μg.h / ml. (2) Compared with the commercially available RH tablets, the peak time was significantly shortened and the peak concentration was significantly increased (P <0.05) after taking RH-SIF tablets, and the area under the curve of AUC in the two formulations were significantly different (P <0.01). ③ Relative bioavailability Frel, ie: AUCT.DR / (AUCR.DT) = 165.68%. CONCLUSION: The two groups of preparations all fit the single-compartment model with a weight of 1 / C2 in rats, and the relative bioavailability of raloxifene was significantly enhanced by the soy isoflavone raloxifene hydrochloride tablets.