PMID: 11908757Mar 23, 2002Paper

The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels

The Pharmacogenomics Journal
R KerbU Brinkmann

Abstract

Phenytoin, an anticonvulsant, exhibits nonlinear pharmacokinetics with large interindividual differences. Because of its small therapeutic range with the risk of therapeutic failure or adverse drug effects in susceptible persons, therapeutic drug monitoring is frequently applied. The interindividual differences in dose response can partially be explained by known genetic polymorphisms in the metabolic enzyme CYP2C9 but a large deal of individual variability remains still unexplained. Part of this variability might be accounted for by variable uptake of phenytoin, which is a substrate of p-glycoprotein, encoded by the human MDR1 gene. We evaluated, whether phenytoin plasma levels correlate with a polymorphism in the MDR1 gene, C3435T, which is associated with intestinal PGP activity. Genotyping and analyses of plasma levels of phenytoin and metabolites in 96 healthy Turkish volunteers showed that the MDR1C > T3435 polymorphism affects phenytoin plasma levels (P = 0.064) and the metabolic ratio of p-HPPH vs phenytoin (MDR1*TT genotype, P = 0.026). The MDR1*CC genotype is more common in volunteers with low phenytoin levels (P < or = 0.001, chi2 test). A combined analysis of variable alleles of CYP2C9, 2C19 and MDR1 revealed that t...Continue Reading

References

Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Sep 1, 1990·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·C Cordon-CardoM R Melamed
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
Oct 1, 1996·Clinical and Experimental Pharmacology & Physiology·M Eichelbaum, B Evert
Oct 1, 1996·Current Opinion in Genetics & Development·M M GottesmanS V Ambudkar
Oct 1, 1996·Pharmacogenetics·M J StubbinsC R Wolf
Feb 1, 1997·Pharmacogenetics·C R BhaskerD J Birkett
Apr 1, 1997·British Journal of Clinical Pharmacology·I IeiriS Higuchi
Mar 10, 1998·European Journal of Biochemistry·A Seelig
Jan 28, 1999·Biochemical and Biophysical Research Communications·U YasarF Sjöqvist
May 20, 1999·Annual Review of Pharmacology and Toxicology·S V AmbudkarM M Gottesman
Aug 25, 1999·Clinical Pharmacology and Therapeutics·A S AynaciogluJ Brockmöller
Oct 6, 1999·British Journal of Clinical Pharmacology·A S AynaciogluI Roots
Dec 2, 1999·Pediatric Neurology·A LazarowskiA Rabinowicz
Sep 6, 2000·Pharmacology·J BrockmöllerI Roots

❮ Previous
Next ❯

Citations

Apr 15, 2010·European Journal of Clinical Pharmacology·Ramasamy KesavanChandrasekaran Adithan
Jun 29, 2010·European Journal of Clinical Pharmacology·Guillermo GervasiniJuan Antonio Carrillo
Nov 5, 2010·International Journal of Clinical Pharmacy·Bob WilffertUNKNOWN KNMP working group Pharmacogenetics
Mar 3, 2011·International Journal of Clinical Pharmacy·Bob WilffertUNKNOWN KNMP working group Pharmacogenetics
Mar 26, 2003·Journal of Psychiatric Research·Manfred Uhr, Markus T Grauer
Oct 31, 2002·Advanced Drug Delivery Reviews·Martin F Fromm
May 6, 2003·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Alex SparreboomWilliam D Figg
Nov 3, 2005·Nature Reviews. Drug Discovery·Russell A WilkeJason H Moore
Feb 1, 2003·Epilepsia·V Ramachandran, Simon D Shorvon
Apr 11, 2003·The New England Journal of Medicine·Timothy A Pedley, Michio Hirano
Apr 11, 2003·The New England Journal of Medicine·Asra SiddiquiSanjay M Sisodiya
Oct 13, 2005·Pharmacogenetics and Genomics·Aurel C AllabiYves Horsmans
Jul 17, 2008·Epilepsia·Wolfgang LöscherDieter Schmidt
Nov 25, 2003·Gut·C G DietrichR P J Oude Elferink
Oct 3, 2002·Annual Review of Pharmacology and Toxicology·Matthias SchwabMartin F Fromm
Jun 29, 2007·Pediatric Research·Diane E AtkinsonStephen W D'Souza
Jun 26, 2004·Clinical Pharmacokinetics·Ichiro IeiriKenji Otsubo
Aug 11, 2004·Clinical Pharmacokinetics·Guillermo GervasiniJulio Benitez
Oct 19, 2011·Biomarkers in Medicine·Tracy A Glauser
Jan 5, 2013·Neurology India·Akanksha N ThakkarUrmila M Thatte
Apr 3, 2012·Pharmacogenomics·Sandeep Grover, Ritushree Kukreti
Oct 20, 2011·Pharmacogenomics·Gianpiero L CavalleriNorman Delanty
Apr 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sarah K TateDavid B Goldstein
Feb 26, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Yvonne G WeberHolger Lerche
Sep 2, 2014·Chemical & Pharmaceutical Bulletin·Feng RenNa Jin
Jul 13, 2004·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Michael L LimAngela D M Kashuba
Jan 30, 2004·Therapeutic Drug Monitoring·Alberto LazarowskiAdrian Rabinowicz
May 29, 2007·Therapeutic Drug Monitoring·Abdel-Hameed I Mohammed EbidSamah A Mohammed
May 12, 2011·Drug Metabolism and Drug Interactions·Alberto Lazarowski, Liliana Czornyj
Oct 4, 2006·Expert Opinion on Drug Metabolism & Toxicology·Ichiro IeiriShun Higuchi
Jan 28, 2014·Expert Opinion on Drug Metabolism & Toxicology·Chiara PianaOscar Della Pasqua
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Jun 4, 2015·Expert Opinion on Drug Metabolism & Toxicology·Valentina Franco, Emilio Perucca
Dec 15, 2015·Seizure : the Journal of the British Epilepsy Association·Anna GuacciGiangennaro Coppola
Sep 22, 2010·Molecular Genetics and Metabolism·Mayumi SaekiMasahiro Tohkin
Oct 1, 2010·Journal of Comparative Pathology·S Van der HeydenR Ducatelle
Nov 26, 2009·La Presse médicale·Pascal Le Corre

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