Mehran Mesgari Abbasi
1,2, Hadi Valizadeh
1, Hamed Hamishekar
1, Leila Mohammadnejad
3, Parvin Zakeri-Milani
4*1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract
Purpose: 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).
Conclusion: 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.