Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance

British Journal of Clinical Pharmacology - Tập 78 Số 2 - Trang 329-342 - 2014
Isabelle Aimone‐Gastin1,2, Noël Zahr3, Amélie Le Gouge4,5, Jean‐Sébastien Hulot3,6, Caroline Houillier7, Khê Hoang‐Xuan7, Emmanuel Gyan8, Séverine Lissandre8, Sylvain Choquet9, Chantal Le Guellec1,2
1Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Tours, Tours, France
2Université François Rabelais de Tours PRES Centre Val de Loire Université EA4245 Tours France
3Service de Pharmacologie CHU Pitié‐Salpêtrière AP‐HP Paris France
4CHRU de Tours Centre d'investigation clinique Tours France
5Université François Rabelais de Tours PRES Centre Val de Loire Université Inserm 202 Tours France
6UPMC Université Paris 06 UMR_S 956 Paris France
7Service de Neurologie CHU Pitié‐Salpêtrière Centre expert national LOC AP‐HP Paris France
8Service d'hématologie et thérapie cellulaire, CHRU de Tours, Tours, France
9Service d'Hématologie CHU Pitié‐Salpêtrière AP‐HP Paris France

Tóm tắt

AimsThe urinary coproporphyrin I/(I + III) ratio may be a surrogate for MRP2 activity. We conducted a prospective study in patients receiving methotrexate (MTX) to examine the relationship between this ratio and the pharmacokinetics of a MRP2 substrate.MethodsThree urine samples were collected from 81 patients for UCP I/(I + III) ratio determination: one before (P1), one at the end of MTX infusion (P2), and one on the day of hospital discharge (P3). Three polymorphisms of ABCC2 were analysed and their relationships with basal UCP I/(I + III) ratio values assessed. All associated drugs were recorded and a drug interaction score (DIS) was assigned. Population pharmacokinetic analysis was conducted to assess whether MTX clearance (MTXCL) was associated with the basal UCP I/(I + III) ratio, its variation during MTX infusion, the DIS or other common covariates.ResultsThe basal UCP I/(I + III) ratio was not associated with ABCC2 polymorphisms and did not differ according to the DIS. Significant changes in the ratio were observed over time, with an increase between P1 and P2 and a decrease at P3 (P < 0.001). No association was found between basal UCP I/(I + III) ratio and MTXCL. The final model indicates that MTXCL was dependent on the change in the ratio between P1 and P3, DIS and creatinine clearance.ConclusionThe basal UCP I/(I + III) ratio is not predictive of MTXCL. However, it is sensitive to the presence of MTX, so it is plausible that it reflects a function modified in response to the drug.

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Tài liệu tham khảo

10.1007/s00280-006-0202-0

10.1111/j.1365-2710.2008.00966.x

10.1111/j.1365-2125.2011.04084.x

10.1002/art.1780330620

10.2165/00003088-197803010-00001

10.1111/bph.12444

10.2133/dmpk.18.91

10.1016/S0014-5793(98)01328-3

10.1124/jpet.104.068536

10.1124/jpet.106.110379

10.1158/0008-5472.CAN-03-4062

10.1586/ecp.11.57

10.1182/blood-2013-01-480335

10.1101/gr.129668.111

10.1200/JCO.2008.20.4156

10.1182/blood-2012-08-452839

10.1182/blood.V100.10.3832

10.1016/j.clpt.2006.08.012

10.1038/tpj.2012.37

10.1097/FPC.0b013e32835c3b24

10.1158/1078-0432.CCR-08-1609

10.1016/j.ejps.2005.12.003

Fuksa L, 2009, Dexamethasone reduces methotrexate biliary elimination and potentiates its hepatotoxicity in rats, Toxicology, 12, 165

10.1007/s11095-009-9896-0

10.1021/jm7015683

10.1155/2011/498757

10.1038/sj.clpt.6100019

10.1200/JCO.2008.20.6300

10.1038/tpj.2010.20

10.1093/ndt/gfr130

10.1097/01.tp.0000235533.29300.e7

Blatt J, 1993, Toxicity following concurrent intrathecal and moderate‐dose intravenous methotrexate, Leukemia, 7, 1734

10.4161/cc.3.12.1331

10.1023/A:1022238506509

10.1124/dmd.109.028282

10.1007/BF02897260

10.1086/508546

10.1111/j.1365-2125.2005.02513.x

10.1097/01.fpc.0000230422.50962.91

10.1007/s00424-006-0109-y

10.1016/j.bcp.2004.10.017

Santucci R, 2010, Severe intoxication with methotrexate possibly associated with concomitant use of proton pump inhibitors, Anticancer Res, 30, 963

Santucci R, 2011, Delayed elimination of methotrexate associated with co‐administration of proton pump inhibitors, Anticancer Res, 30, 3807

10.1074/jbc.M708615200

10.1016/j.bcp.2005.03.001

10.1161/CIRCULATIONAHA.105.576850

10.1124/dmd.105.008938

10.1016/j.jchromb.2009.09.047

Saada S, 2012, [Adaptation of methotrexate determination in serum with Unicel DxC600((R))], Ann Biol Clin (Paris), 70, 277

10.1016/j.cmpb.2007.12.002

10.1007/s11095-006-9067-5

10.1016/S0169-2607(98)00098-4

10.1038/nature02168

Frank M, 1990, Diagnostic and pathogenetic implications of urinary coproporphyrin excretion in the Dubin‐Johnson syndrome, Hepatogastroenterology, 37, 147

10.1086/302292

10.1097/FPC.0b013e3282f974b7

10.1038/bjc.1992.83

10.1016/j.phrs.2004.09.005

Aubel RA, 1998, Adenosine triphosphate‐dependent transport of anionic conjugates by the rabbit multidrug resistance‐associated protein Mrp2 expressed in insect cells, Mol Pharmacol, 53, 1062

10.1002/bdd.678

10.1111/j.1365-2125.2008.03303.x

10.3109/00498254.2011.578761

Chen ZS, 2002, Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system, Cancer Res, 62, 3144

10.1124/jpet.107.121491

Masuda M, 1997, Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats, Cancer Res, 57, 3506

10.1124/jpet.106.101774

10.1158/1078-0432.CCR-08-2940

10.1158/1535-7163.MCT-09-0668

10.1097/01213011-200505000-00002

Maia MB, 1996, In vitro and in vivo protein binding of methotrexate assessed by microdialysis, Int J Clin Pharmacol Ther, 34, 335

10.1111/j.1440-1681.1982.tb00800.x

Skibinska L, 1990, Methotrexate binding to human plasma proteins, Pol J Pharmacol Pharm, 42, 151

10.1200/JCO.1994.12.8.1667

Woillard JB, 2013, An innovative model of time‐dependant methotrexate elimination, Fundam Clin Pharmacol, 27, 20

10.1055/s-2005-837780

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British Journal of Clinical Pharmacology

Tập 78 Số 2

329-342

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