PT - JOURNAL ARTICLE AU - Lindenmaier, Heike AU - Becker, Melanie AU - Haefeli, Walter Emil AU - Weiss, Johanna TI - INTERACTION OF PROGESTINS WITH THE HUMAN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 (MRP2) AID - 10.1124/dmd.105.005314 DP - 2005 Nov 01 TA - Drug Metabolism and Disposition PG - 1576--1579 VI - 33 IP - 11 4099 - http://dmd.aspetjournals.org/content/33/11/1576.short 4100 - http://dmd.aspetjournals.org/content/33/11/1576.full SO - Drug Metab Dispos2005 Nov 01; 33 AB - Progestins are widely used as oral contraceptives and hormone replacement therapy. Recently it has been demonstrated that many progestins are inhibitors of P-glycoprotein, possibly explaining gender differences in drug actions. In vitro evidence suggested that at least norgestimate might also inhibit other transporters like the multidrug resistance-associated protein 2 (MRP2). We therefore investigated whether norgestimate, desogestrel, medroxyprogesterone acetate, norethisterone, progesterone, cyproterone acetate, chlormadinone acetate, and levonorgestrel inhibit MRP2 in vitro using confocal laser scanning microscopy and 5-chloromethylfluorescein diacetate as a prodrug of the fluorescent 5-chloromethylfluorescein (CMF), which is actively transported by MRP2 as glutathione conjugate. Of the progestins tested, only norgestimate (50 μM) and progesterone (100 μM) significantly increased intracellular CMF fluorescence by 62% and 53%, respectively. In conclusion, the progestins norgestimate and progesterone significantly inhibit the transport activity of MRP2 in vitro. The American Society for Pharmacology and Experimental Therapeutics