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Involvement of multidrug resistance proteins (MRPs) in the efflux of vardenafil

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Abstract

In the present study, we examined the roles of specific multidrug resistance proteins (MRPs) in the efflux transport of the phosphodiesterase type 5 inhibitors, vardenafil and sildenafil. Using MDCKII cells overexpressing MRP1, MRP2, and MRP3 (MDCKII-MRP1, -MRP2, and MRP3, respectively) as model systems, we measured the basal to apical and apical to basal transport of vardenafil and sildenafil at concentrations ranging from 1 to 100 μM. Vardenafil had a much greater basal to apical than apical to basal transport rate in MDCKII-MRP1, -MRP2, and MRP3 cells, suggesting that vardenafil is a substrate for MRP1, MRP2, and MRP3. In contrast, the basal to apical and apical to basal transport rate were similar to each other in each of the MRPs-overexpressing MDCKII cells, indicating that sildenafil was not pumped out via MRP1, MRP2, and MRP3. Vardenafil efflux from MDCKII-MRP1, MRP2, and MRP3 cells was concentration dependent and occurred with K m values of 48.2 ± 15.5, 12.8 ± 4.18, and 14.1 ± 7.4 μM, respectively. In conclusion, MRP1, MRP2, and MRP3 may influence the absorption, disposition, and cellular accumulation of vardenafil, but not sildenafil.

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Acknowledgments

The present research was conducted by a Grant (10033664) from the Ministry of Knowledge and Economy, Korea and by Basic Science Research Program (2010-0005370), Ministry of Education, Science and Technology, Korea.

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Authors and Affiliations

  1. College of Pharmacy, Dankook University, Cheonan, 330-714, Korea

    Min-Koo Choi

  2. College of Pharmacy, Kyungpook National University, Daegu, 702-701, Korea

    Im-Sook Song

  3. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, 614-735, Korea

    Im-Sook Song

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  1. Min-Koo Choi
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  2. Im-Sook Song
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Correspondence to Im-Sook Song.

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Choi, MK., Song, IS. Involvement of multidrug resistance proteins (MRPs) in the efflux of vardenafil. Journal of Pharmaceutical Investigation 42, 65–70 (2012). https://doi.org/10.1007/s40005-012-0012-9

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  • DOI: https://doi.org/10.1007/s40005-012-0012-9

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