盐酸青藤碱控释微丸在Beagle犬体内药物动力学研究

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-0．05mol·L^-1磷酸二氢铵溶液（50：12：190），柱温为30℃，流速为0．7mL·min^-1；检测波长为264nm；结果盐酸青藤碱在50—4000ng·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=0．9964，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，（1738±396）ng·mL^-1；Tmax：（6．2±1．1）h，（7．0±1．0）h；AUC0-1（20．2±3．3）h·ug·mL^-1，（22．8±5．0）h·ug·mL^-1，相对生物利用度为（90．1±10．4）％。结论盐酸青藤碱控释微丸在Beagle犬体内血药浓度曲线平稳，维持时间长，控释效果较好，达到了预期的目标。

Pharmacokinetics of Sinomenine Hydrochloride Controlled-release Pellets in Beagle Dogs

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-aeetonitrile -0.05 mol·L^-1 ammonium dihydrogen phosphate solution （50： 12： 190） , colunm 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 hydroehloride to IS and drug concentration was good,R = 3.6 × 10^-4 C ＋ 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, AUC0-1 （20.2 ± 3.3 ） and （22.8 ± 5.0） h·ug·mL^-1 for test and reference preparations, respectively. The relative bioavailability was（90.1 ± 10.4 ）%. CONCLUSION The concentration-time curve of sinomenine hydroehloride controlledrelease pellets in Beagle dogs was flatter and the duration was longer. The present studies achieved our prospective aims.