The Effects of Cetirizine on P-glycoprotein Expression and Function In vitro and In situ.

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Mesgari Abbasi M, Valizadeh H, Hamishekar H, Mohammadnejad L, Zakeri-Milani P

The Effects of Cetirizine on P-glycoprotein Expression and Function In vitro and In situ.

Adv Pharm Bull. 2016 Mar;6(1):111-8. doi: 10.15171/apb.2016.017. Epub 2016 Mar 17.

PubMed ID

27123426 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cetirizine	ATP-dependent translocase ABCB1	Protein	Humans	No	Substrate Inhibitor	Details