盐酸青藤碱控释微丸在Beagle犬体内药物动力学研究

Pharmacokinetics of Sinomenine Hydrochloride Controlled-release Pellets in Beagle Dogs

关键词:  盐酸青藤碱  微丸  高效液相色谱法  药物动力学

Key words:  sinomenine hydrochloride  pellets  HPLC  pharmacokinetics

摘要:

目的测定盐酸青藤碱控释微丸在Beagle犬体内药物动力学参数，计算相对生物利用度。方法采用反相高效液相色谱法，流动相为甲醇-乙腈-0.05 mol·L-1磷酸二氢铵溶液（50∶12∶190），柱温为30 ℃，流速为0.7 mL·min-1；检测波长为264 nm；结果盐酸青藤碱在50～4 000 ng·mL-1内，主药与内标峰面积比（R）与浓度（C）间线性关系良好，线性方程为R=3.6×10-4C＋0.02，r=0.996 4，方法的精密度和回收率均符合中国药典2005版二部的规定。受试制剂和参比制剂的主要药物动力学参数分别为：t1/2：(19.9±4.3)h,(17.8±2.1)h；Cmax：(638±128)ng·mL-1，(1 738±396)ng·mL-1；Tmax：(6.2±1.1)h，(7.0±1.0)h；AUC0～t：(20.2 ±3.3)h·μg·mL-1，(22.8±5.0)h·μg·mL-1，相对生物利用度为（90.1±10.4）%。

Abstract:

OBJECTIVE To determine pharmacokinetic parameters of sinomenine hydrochloride controlled-release pellets in Beagle dogs and calculate the relative bioavailability.METHODS To use a high performance liquid chromatography (HPLC) method with the mobile phase consisted of methanol-acetonitrile -0.05 mol·L-1 ammonium dihydrogen phosphate solution (50∶12∶190), column temperature was 30 ℃, flow rate of mobile phase was 0.7 mL·min-1 and wavelength of detector was set at 264 nm. RESULTS In the range of 50-4 000 ng·mL-1, the linear between peak-area ratios of sinomenine hydrochloride to IS and drug concentration was good,R=3.6×10-4C＋0.02，r=0.996 4. The precision and recovery were fit for Ch.P(2005)Vol Ⅱ. The pharmacokinetic parameters were t1/2（19.9±4.3）and（17.8±2.1）h,Cmax(638±128)and（1 738±396） ng·mL-1,Tmax（6.2±1.1） and（7.0±1.0）h, AUC0～t（20.2 ±3.3） and（22.8±5.0） h·μg·mL-1 for test and reference preparations, respectively. The relative bioavailability was（90.1±10.4）%.CONCLUSION The concentration-time curve of sinomenine hydrochloride controlled-release pellets in Beagle dogs was flatter and the duration was longer. The present studies achieved our prospective aims.