A self-contrast approach to evaluate the inhibitory effect of chrysosplenetin, in the absence and presence of artemisinin, on the in vivo P-glycoprotein-mediated digoxin transport activity

作者：Yang, Bei; Ma, Li-Ping; Ma, Wei; Wei, Shi-Jie; Ji, Hong-Yan; Li, Hou-Gang; Dang, Hong-Wan; Liu, Cheng; Wu, Xiu-Li; Chen, Jing^*

来源：Biomedical Chromatography, 2016, 30(10): 1582-1590.

DOI：10.1002/bmc.3725

• self-contrast
• chrysosplenetin
• P-glycoprotein
• artemisinin
• UHPLC-MS
• MS

In this study, we used a self-contrast method, which excluded the individual difference, to evaluate the inhibitory effect of chrysosplentin (CHR) in the presence or absence of artemisinin (ART) on the P-glycoprotein (P-gp) transport activity. A sensitive and rapid UHPLC-MS/MS method was applied for quantification of digoxin, a P-gp-specific substrate, in rat plasma. A pharmacokinetic study was carried out: first after an oral administration of digoxin at a dose of 0.09mg/kg (first period), followed by a 20-day wash-out, then after another administration of digoxin (second period). During the second period, test compounds were orally given three times per day for seven consecutive days. Results showed that the t(1/2) of digoxin in all the groups had no significant difference between the first and second periods. The AUC(0-24), C-max, t(max), and Cl-z/F of the negative control and ART alone groups showed no difference. However, the AUC(0-24) and C-max in the CHR alone, CHR-ART (1:2) and verapamil (positive control) groups showed 2.34-, 3.04-, 1.79-, and 1.81-, 1.99-, 2.06-fold increases along with 3.50-, 3.84- and 4.76-fold decreases for CLz/F, respectively. The t(max) in the CHR-ART (1:2) group increased 3.73-fold. In conclusion, our self-contrast study suggested that CHR, especially when combined with ART in a ratio of 1:2, inhibited P-gp activity while ART alone has no effect.

• 出版日期2016-10
• 单位宁夏医科大学