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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
Author(s) -
Yang Bei,
Ma LiPing,
Ma Wei,
Wei ShiJie,
Ji HongYan,
Li HouGang,
Dang HongWan,
Liu Cheng,
Wu XiuLi,
Chen Jing
Publication year - 2016
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3725
Subject(s) - digoxin , cmax , chemistry , pharmacokinetics , artemisinin , pharmacology , p glycoprotein , verapamil , in vivo , oral administration , medicine , biochemistry , antibiotics , plasmodium falciparum , immunology , malaria , multiple drug resistance , heart failure , microbiology and biotechnology , biology , organic chemistry , calcium
Abstract 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 © 2016 John Wiley & Sons, Ltd.