白芍总苷在急性CCl_4肝损伤大鼠与正常大鼠体内的药代动力学比较研究  

Pharmacokinetic Study of Total Glucosides of Paeony in Rats with Acute Liver Injury and Normal Rats

作　　者：刘恩荔[1] 谢敏[2] 王玉峰[3] 李向军[3] 牛丽颖[2] 

机构地区：[1]山西医科大学药学院,太原030001 [2]河北医科大学中医学院河北省实验动物重点实验室,石家庄050091 [3]石家庄以岭药业股份有限公司,石家庄050035

出　　处：《中国药学杂志》2012年第7期534-538,共5页Chinese Pharmaceutical Journal

基　　金：河北省自然科学基金资助项目(C2010000498)

摘　　要：目的比较白芍总苷在急性CCl4肝损伤大鼠与正常大鼠体内药物动力学过程的异同,为临床合理用药提供参考。方法采用一次性腹腔注射CCl4建立大鼠急性肝损伤模型,采用HPLC测定模型大鼠和正常大鼠灌胃给予白芍总苷后,不同时间点的Pae和Alb的血药浓度,根据药-时曲线计算药代动力学参数。结果在模型组大鼠体内,白芍总苷中芍药苷(Pae)和芍药内酯苷(Alb)在高、中、低剂量(0.047、0.141、0.282 g.mL-1)时的t1/2分别为5.02、4.52、4.91 h;5.22、5.04、5.05 h。ρmax分别为22.54、14.52、5.49μg.mL-1;9.02、5.04、2.34μg.mL-1。AUC0-t分别为(146.55±7.52)、(84.14±7.84)、(31.62±2.97)μg.h.mL-1;(56.56±8.70)、(32.18±3.49)、(13.48±1.66)μg.h.mL-1。tmax均为2 h。在正常大鼠体内,Pae和Alb在高、中、低剂量(0.047、0.141、0.282 g.mL-1)时的t1/2分别为3.95、3.69、3.95 h;3.74、3.98、3.79 h。ρmax分别为19.16、11.60、4.46μg.mL-1;7.16、4.00、1.93μg.mL-1。AUC0-t分别为(116.26.6±19.99)、(67.74±12.79)、(25.01±2.62)μg.h.mL-1;(45.03±5.84)、(27.26±3.57)、(10.59±1.86)μg.h.mL-1。tmax为2.5 h。结论与正常组比较,模型组的ρmax、AUC0-t显著增大,t1/2延长,tmax明显缩短。模型组和正常组的tmax和t1/2不受白芍总苷剂量影响,但剂量与ρmax和AUC0-t具一定的相关性。OBJECTIVE To compare the pharmacokinetics of total glucosides of paeony （TGP） in rats with acute liver injury and normal rats, thus to provide evidence for determining dosage regimen in clinic. METHODS Acute liver injury rat model was established by single CCl4 intraperitoneal injection. Three dosages of TGP were orally administered to normal and model rats. The concentrations of Pae and Alb in plasma at different time after dosing were determined with HPLC method. The pharmacokinetic parameters were calculated based on mean plasma concentration-time curves of Pae and Alb. RESULTS In model rat group, the t1/2of Pae and Alb at high, medium, and low dosage （0. 047, 0. 141,0. 282 g . mL-1 ）were 5.02, 4. 52, 4. 91 h and 5.22, 5.04, 5.05 h, respectively. The Pm,xOf Pae and Alb of TGP at different dosages were 22. 54, 14. 52, 5.49 ug . mL-1 , and 9. 02, 5.04, 2. 34 ug .mL-1 , respectively. The AUC0-t of Pae and Alb of TGP at different dosages were （ 146. 55 ± 7.52）, （ 84. 14 ± 7.84）, （ 31.62 ± 2. 97 ） ug . h. mL -1, and （56. 56 ±8.70） , （32. 18 ±3.49） , （ 13.48 ± 1.66） ug . h . mL-1 , respectively. The tmax of paeoniflorin（Pae） and albiflorin （Alb） of TGP at different dosages were both 2 h. In rats of normal group, the t1/2 of Pae and Alb of TGP at different dosages respectively were 3.95, 3.69, 3.95 h, and 3.74, 3.98, 3.79 h, respectively. The pmax were 19. 16, 11.60, 4.46 ug . mL-1, and 7. 16, 4.00, 1.93 ug.mL L, respectively. TheAUC0-t were （116.26.6±19.99）, （67.74±12.79）, （25.01 ±2.62） ug. h. mL-1 , and （45.03 ±5.84）, （27.26 ±3.57）, （10. 59 ± 1.86） ug . h . mL-1 , respectively. The tmax were both 2. 5 h. CONCLUSION Compared with normal group, the pmax and AUC0-t of TGP in model group significantly increased, t max decreased, and t1/2 prolonged ;tmax and t1/2： had no difference among three dosages, and Pmax. and AUC0-t had correlation with dosage.

关 键 词：白芍总苷 芍药苷 芍药内酯苷 药代动力学 肝脏损伤模型 

分 类 号：R965.1[医药卫生—药理学]