Study on pharmacokinetics-pharmacodynamics correlation of Danshensu in rats with focal cerebral ischemia.
- Author:
Jin-Chao AI
;
Hui-Fen ZHOU
;
Ming-Chun SHU
;
Liu-Ling DAI
;
Lu ZHENG
;
Yu-Yan ZHANG
;
Jie-Hong YANG
;
Xian-Bin WU
;
Hai-Tong WAN
- Publication Type:Journal Article
- MeSH:
Animals;
Brain Ischemia;
drug therapy;
Drugs, Chinese Herbal;
pharmacokinetics;
pharmacology;
therapeutic use;
Male;
Rats;
Rats, Sprague-Dawley;
Salvia miltiorrhiza;
chemistry
- From:
China Journal of Chinese Materia Medica
2014;39(14):2751-2755
- CountryChina
- Language:Chinese
-
Abstract:
To study the pharmacokinetic process of Danshensu in cerebal ischemia injury model rats and the correlation with its anti-cerebral ischemia effect. In this study, the middle cerebral artery occlusion (MCAO) model was established, in which all of the rats were intravenously injected of Danshensu at a single dose of 40 mg x kg(-1). The HPLC-DAD method was applied to determine the plasma concentration of Danshensu at different time points and draw the drug-time curve. Meanwhile, the superoxide dismutase (SOD) and the lactate dehydrogenase (LDH) activity were determined to draw the time-effect curve. The DAS 3.2. 6 software was used to process the data, analyze their correlation, compare the pharmacokinetic difference between model and normal rats after the administration of the same doses of Danshensu and the changes in pharmacodynamic indicators of model rats after the administration, and evaluate the effect of Danshensu in treating the cerebral ischemia disease. According to the results, the pharmacokinetic processes of Danshensu in the cerebral ischemia-reperfusion and normal rats were consistent to the two-compartment model. The main pharmacokinetic parameters were: t1/2alpha were (0.267 +/- 0.026), (0.148 +/- 0.020) h;t1/2beta were (1.226 +/- 0.032), (1.182 +/- 0.082) h; AUC0-infinity were (42.168 +/- 4.007), (26.881 +/- 1.625) mg x L(-1) x h. After the cerebral ischemia-reperfusion, the activity of SOD decreased and the activity of LDH increased. Danshensu could inhibit the decrease in the SOD activity and the increase in the LDH activity within a certain period of time. This indicated that Danshensu could stay longer in cerebral ischemia-reperfusion rats than in normal rats and eliminated more slowly, which reflected the rationality of Danshensu in the clinical treatment of cerebral ischemia diseases. Danshensu's effect against the cerebral ischemic injury may be related with its level in vivo. Its plasma concentration is positively related to the SOD activity and negatively related to the LDH activity.
