Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 12، دوره 19، شماره 4، تیر 2016، صفحه 423-429 اصل مقاله (1.14 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2016.6815 | ||
| نویسندگان | ||
| Mehran Mesgari Abbasi1، 2؛ Hadi Valizadeh1؛ Hamed Hamishekar1؛ Leila Mohammadnejad3؛ Parvin Zakeri-Milani* 4 | ||
| 1Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 2Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 3Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 4Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| چکیده | ||
| Objective(s):Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It is important to understand which drugs are substrates, inhibitors, or inducers of P-gp to minimize or avoid unwanted interactions. The aim of this study was to investigate the effects of clemastine on the expression and function of P-gp. Materials and Methods: The effect of clemastine on P-gp function and expression was evaluated in vitro byrhodamine-123 (Rho123) efflux assay in Caco-2 cells and Western blot analysis. Rat in situ single pass intestinal permeability model was used to investigate the clemastine effect on digoxin Peff, as a known P-gp substrate. Digoxin levels in intestinal perfusates were assayed by high performance liquid chromatography (HPLC) method. Results:The Caco-2 intracellular accumulation of Rho123 in clemastine and verapamil treated cells was 90.8 ± 9.8 and 420.6±25.4 pg/mg protein, respectively which was significantly higher than that in control cells (50.2±6.0; P<0.05). Immunoblotting results indicated that clemastine decreased expression of P-gp in Caco-2 cells in vitro. More over effective intestinal permeability (Peff) of digoxin in the presence of clemastine, was significantly increased compare to control group. Conclusion: Findings of our study suggested dose dependent P-gp inhibition activity for clemastine in vitro and in situ. Therefore co-administration of clemastine with P-gp substrates may result in unwanted interactions and side effects. | ||
| کلیدواژهها | ||
| Clemastine؛ Digoxin؛ Intestinal Absorption؛ P-glycoprotein | ||
| مراجع | ||
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