Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans

Gießmann, Thomas; May, Karen; Modeß, Christiane; Wegner, Danilo; Hecker, Ute; Zschiesche, M; Dazert, Peter; Grube, Markus; Schroeder, Eike; Warzok, R

doi:10.1016/j.clpt.2004.04.011

Cited by 158 publications

(150 citation statements)

References 31 publications

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“…Induction of intestinal and/or hepatic MRP2 has been implicated to play a role in the interactions observed clinically between rifampin and morphine, mycophenolate mofetil, ezetimibe, and carvedilol (Fromm et al, 1997;Giessmann et al, 2004b;Oswald et al, 2006). Carbamazepine also increased talinolol elimination in humans, most likely by induction of P-gp and MRP2 (Giessmann et al, 2004a). Cho et al (2011) reported an induction of SLC22A1 mRNA encoding the uptake transporter OCT1 by rifampin in peripheral blood cells and enhanced glucose-lowering effects of metformin during rifampin administration.…”

Section: Induction Of Uptake and Efflux Transportersmentioning

confidence: 99%

Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects

2013

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Section: Induction Of Uptake and Efflux Transportersmentioning

confidence: 99%

Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects

2013

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“…Finally, dysembryoplastic neuroepithelial tumors from patients undergoing AED treatment with various combinations of carbamazepine, oxcarbazepine, tiagabine, and lamotrigine, also exhibit increased MRP2 and MRP5 protein expression, compared with peritumoral tissue or samples obtained from patients diagnosed with arteriovenous malformations (Vogelgesang et al, 2004). Given that some AED medications are known to upregulate transporter expression in peripheral compartments [e.g., carbamazepine-induced induction of intestinal MRP2 mRNA and protein expression (Giessmann et al, 2004)], it is unclear whether the altered transporter expression observed in these various studies is due to the underlying disease, the therapies used to treat the disease, or a combination of the two.…”

Section: A Epilepsymentioning

confidence: 99%

Multidrug Resistance-Associated Proteins: Expression and Function in the Central Nervous System

Dallas

Miller²,

Bendayan³

2006

Pharmacol Rev

267

207

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“…It was also detected in renal brush-border membranes, the intestine (Schaub et al, 1997), placenta (St.-Pierre et al, 2000;Gerk and Vore, 2002), and brain (Török et al, 2003). In human carcinoma, MRP2 may confer resistance to chemotherapy (Norris et al, 1996;Nies et al, 2001;Young et al, 2001;Schinkel and Jonker, 2003), and it appears also to play a role in drug-drug interactions (Fromm et al, 2000;Bramow et al, 2001;Bode et al, 2002;Huisman et al, 2002;Giessmann et al, 2004).…”

mentioning

confidence: 99%

Interaction of Progestins With the Human Multidrug Resistance-Associated Protein 2 (Mrp2)

Lindenmaier

Becker²,

Haefeli³

et al. 2005

Drug Metab Dispos

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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 M) and progesterone (100 M) 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.Multidrug resistance-associated proteins (MRPs) are a subfamily of the ATP-binding cassette transport protein family involved in drug resistance (Schinkel and Jonker, 2003). MRP2 is a key member of this group and was identified in the canalicular membrane of hepatocytes as a transporter for organic anions extruding a wide range of glutathione, glucuronate, and sulfate conjugates into the bile (Ishikawa 1993;Ito et al., 1997;Paulusma and Oude Elferink, 1997). It was also detected in renal brush-border membranes, the intestine (Schaub et al., 1997), placenta (St.-Pierre et al., 2000;Gerk and Vore, 2002), and brain (Török et al., 2003). In human carcinoma, MRP2 may confer resistance to chemotherapy (Norris et al., 1996;Nies et al., 2001;Young et al., 2001;Schinkel and Jonker, 2003), and it appears also to play a role in drug-drug interactions (Fromm et al., 2000;Bramow et al., 2001;Bode et al., 2002;Huisman et al., 2002;Giessmann et al., 2004).In recent years it has been suggested that gender could alter the activity of drug transporters like P-glycoprotein (P-gp) (Cummins et al., 2002). Hence in a previous study we have investigated whether P-gp is inhibited by progestins used in oral contraceptives and hormone replacement therapy. All progestins tested had P-gp inhibitor properties, with some of them being as potent as the well known P-gp inhibitor quinidine (Fröhlich et al., 2004). Interestingly, one of the tested progestins (norgestimate) revealed an inhibitory effect on the transport of calcein-acetoxymethylester (calcein-AM) not only in the P-gp-overexpressing cell line L-MDR1, but also in the parental cell line LLC-PK1, which only expresses low amounts of P-gp (Decorti et al., 2001;Weiss et al., 2003;Fröhlich et al., 2004), indicating that this effect was not selective. Because LLC-PK1 expresses MRP2 (Evers et al., 1996;Decorti et al., 2001) and MRP2 can transport calcein-AM (Evers et al., 2000), these data may suggest that norgestimate also...

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Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans

Abstract: Aside from induction of CYP3A4, carbamazepine acts as an inducer of intestinal MDR1 mRNA, MRP2 mRNA, and MRP2 protein content.

Cited by 158 publications

References 31 publications

Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects

Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects

Multidrug Resistance-Associated Proteins: Expression and Function in the Central Nervous System

Interaction of Progestins With the Human Multidrug Resistance-Associated Protein 2 (Mrp2)

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