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

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• 作者：Bei Yang ; Li-Ping Ma ; Wei Ma ; Shi-Jie Wei ; Hong-Yan Ji ; Hou-Gang Li ; Hong-Wan Dang ; Cheng Liu ; Xiu-Li Wu and Jing Chen
• 刊名：Biomedical Chromatography
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：30
• 期：10
• 页码：1582-1590
• 全文大小：386K
• ISSN：1099-0801

文摘

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 0.09 mg/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 CL_z/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. Copyright