Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2).

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Lindenmaier H, Becker M, Haefeli WE, Weiss J

Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2).

Drug Metab Dispos. 2005 Nov;33(11):1576-9. Epub 2005 Jul 27.

PubMed ID

16049127 [ View in PubMed

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Abstract

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 microM) and progesterone (100 microM) 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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Norgestimate	Canalicular multispecific organic anion transporter 1	Protein	Humans	Unknown	Inhibitor	Details
Norgestimate	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details