title: 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.
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 t1/2 of digoxin in all the groups had no significant difference between the first and second periods. The AUC0-24 , Cmax , tmax , and Clz /F of the negative control and ART alone groups showed no difference. However, the AUC0-24 and Cmax 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 tmax 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.
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Bei
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Institute of Clinical Pharmaco, General Hospital of Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Wei
authors.affiliation: Institute of Clinical Pharmaco, General Hospital of Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Hou-Gang
authors.initials: HG
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmaco, General Hospital of Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Hong-Wan
authors.initials: HW
authors.lastname: Dang
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D037621:Artemisinins / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D004077:Digoxin / Q000008:administration & dosage / Q000378:metabolism*; D005419:Flavonoids / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D053719:Tandem Mass Spectrometry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D037621:Artemisinins; D005419:Flavonoids; C472159:chrysoplenetin; D004077:Digoxin; C031327:artemisinin
keywords: P-glycoprotein; UHPLC-MS/MS; artemisinin; chrysosplenetin; self-contrast