Impact of the changes in P-glycoprotein activity on domperidone pharmacokinetics in rat plasma.
The effect of quinidine (QD) and grapefruit juice (GFJ) extract, P-glycoprotein inhibitors, on the domperidone (DOM) concentration in rat plasma was investigated. DOM, a dopamine D(2)-receptor antagonist is a substrate for P-glycoprotein. DOM(10 mg/kg) was administered orally 2 h after GFJ extract (0.2 ml/kg) or QD (25 mg/kg). DOM concentration in plasma samples was determined by HPLC with fluorescence detection. The GFJ extract and QD administration significantly increased c(max) of DOM by 19% and 36%, respectively, and the AUC(0-0.25) (area under the concentration-time curve from time zero to 15 min) by 29% and 44%, respectively. In addition, QD significantly increased the DOM AUC(0-2) (32%), whereas 19% increase was observed after GFJ extract administration. In conclusion, GFJ and QD significantly influenced DOM rat plasma concentration during the first two hours after DOM administration indicating that interaction takes place during absorption phase.
Bamburowicz-Klimkowska
Magdalena
M
Department of Toxicology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, PL 02-097 Warszawa, Poland. mjbamburowicz@op.pl
Zywiec
Katarzyna
K
Potentas
Agata
A
Szutowski
Mirosław
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D001628:Beverages; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002957:Citrus; D004294:Domperidone / Q000097:blood / Q000493:pharmacokinetics*; D018492:Dopamine Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D018565:Food-Drug Interactions; D007408:Intestinal Absorption; D008297:Male; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018492:Dopamine Antagonists; D004294:Domperidone; D011802:Quinidine