The Effects of Cetirizine on P-glycoprotein Expression and Function In vitro and In situ.
OBJECTIVE
P-glycoprotein (P-gp) plays a major role in oral absorption of drugs. Induction or inhibition of P-gp by drugs contributes to variability of its transport activity and often results in clinically relevant drug-drug interactions. The purpose of this study was to investigate the effect of cetirizine, a second generation H1 antihistamine, on P-gp function and expression in vitro and in situ.


METHODS
The in-vitro rhodamin-123 (Rho123) efflux assay in Caco-2 cells was used to study the effect of cetirizine on P-gp function. Western blot analysis was used for surveying the effect of cetirizine on expression of P-gp in Caco-2 cells. Rat in situ single-pass intestinal permeability technique was used to calculate the intestinal permeability of a known P-gp substrate (digoxin) in the presence of cetirizine. The amounts of digoxin and cetirizine in intestinal perfusion samples were analyzed using a HPLC method.


RESULTS
The results showed significant increase in Rho123 uptake (P < 0.05) and also P-gp band intensity decrease in cetirizine-treated cells in vitro. Furthermore the intestinal permeability of digoxin was also increased significantly in the presence of cetirizine (P < 0.01).


CONCLUSIONS
Therefore it is concluded that cetirizine is a P-gp inhibitor and this should be considered in co administration of cetrizine with other P-gp substrate drugs. Further investigations are required to confirm our results and to determine the mechanism underlying P-gp inhibition by cetirizine.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Mehran
M
Mesgari Abbasi
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Hadi
H
Valizadeh
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Hamed
H
Hamishekar
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Leila
L
Mohammadnejad
Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Parvin
P
Zakeri-Milani
Cetirizine; Digoxin; Intestinal permeability; P-glycoprotein