RT Journal Article
SR Electronic
T1 INTERACTION OF PROGESTINS WITH THE HUMAN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 (MRP2)
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1576
OP 1579
DO 10.1124/dmd.105.005314
VO 33
IS 11
A1 Heike Lindenmaier
A1 Melanie Becker
A1 Walter Emil Haefeli
A1 Johanna Weiss
YR 2005
UL http://dmd.aspetjournals.org/content/33/11/1576.abstract
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