丹参酮ⅡA对茶碱在大鼠体内药动学特征的影响

Effects of TanshinoneⅡA on the Pharmacokinetics of Theophylline in Rats

目的研究丹参酮ⅡA对大鼠体内茶碱药动学特征的影响。方法将24只大鼠随机分成3组,Ⅰ组:生理盐水,ip×7 d;Ⅱ组:丹参酮ⅡA 7 mg·kg?1·d?1,ip×7 d;Ⅲ组:丹参酮ⅡA 20 mg·kg?1·d?1,ip×7 d。于第7天给药后3组均灌胃给予氨茶碱(20.8 mg·kg?1),分别于给药前后的0.17,0.33,0.5,1.0,1.5,2.0,4.0,6.0,8.0,10.0,12.0 h尾静脉采血。用HPLC测定血浆中茶碱的血药浓度,并用DAS计算药动学参数。结果茶碱在大鼠体内主要药动学参数,Cmax为(29.43±1.53)mg·L?1、AUC0→∞为(156.95±10.22)mg·h·L?1、MRT0-∞为(4.44±0.42)h、CLz/F为(0.13±0.01)L·h?1·kg?1。与Ⅰ组比较,Ⅱ组各参数无显著性差异,Ⅲ组主要参数AUC0→12h、AUC0→∞、Cmax、MRT0-t、MRT0-∞、CLz/F等有显著性差异(P<0.05),其中Cmax、AUC0→∞分别下降了7.54%和14.69%,CLz/F增加了23.08%。结论高剂量的丹参酮ⅡA能影响茶碱在大鼠体内药动学特征,而低剂量无影响。

OBJECTIVE To study the effects of tanshinone Ⅱ A on the pharmacokinetics of theophylline in rats. METHODS A total of 24 rats were randomly divided into three groups： Group Ⅰ（the same volume of saline, ip×7 d）, Group Ⅱ（tanshinoneⅡA 7 mg·kg-1·d-1, ip×7 d） and Group Ⅲ（tanshinoneⅡA 20 mg·kg-1·d-1, ip×7 d）. The 3 groups were given a single dose of 20 mg·kg-1·d-1 aminophylline with intragastric administration after intraperitoneal injection for 7 d. Blood samples were collected from the tail vein before administration and at 0.17, 0.33, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0 and 12.0 h points after administration. The concentration of theophylline in plasma was detected by HPLC method. The pharmacokinetic parameters were analyzed by DAS program. RESULTS After administration, the main pharmacokinetic parameters of theophylline for Group Ⅰ were as follows respectively： Cmax was（29.43±1.53） mg·L-1, AUC0→∞ was（156.95±10.22） mg·h·L-1, MRT0-∞ was（4.44±0.42）h, CLz/F was（0.13±0.01）L·h-1·kg-1. Compared with Group Ⅰ, there was no significant difference in the pharmacokinetic parameters of theophylline for Group Ⅱ, but the AUC0→12 h, AUC0→∞, Cmax, MRT0-t, MRT0-∞, CLz/F of theophylline for Group Ⅲ were a significant difference（P〈0.05）. The Cmax and AUC0→∞ of theophylline for Group Ⅲdecreased 7.54% and 14.69%, respectively and the CLz/F was increased 23.08%. CONCLUSION The higher dosage of tanshinoneⅡA affects the pharmacokinetics of theophylline in rats, while the lower dosage does not.