Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine

Drug Metabolism and Drug Interactions

Volumn 26, Issue 1, 2011, Pages 5-12

  López, Marisol ^a   Dorado, Pedro ^b   Monroy, Nancy ^c   ElisaAlonso, María ^c   Jung Cook, Helgi ^c,d   MacHín, Esther ^b   Peñas Lledó, Eva ^b   Llerena, Adrián ^b  

^a DEPARTAMENTO DE SISTEMAS BIOLÓGICOS   (Mexico)

^b UNIVERSITY OF EXTREMADURA   (Spain)

^c NATIONAL INSTITUTE OF NEUROLOGY AND NEUROSURGERY   (Mexico)

^d UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

Author keywords

antiepileptic drug; cytochrome P450; lamotrigine; pharmacogenetics; phenytoin; UDP glucuronosyltransferase (UGT)

Indexed keywords

AMITRIPTYLINE; CARBAMAZEPINE; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A4; IMIPRAMINE; LAMOTRIGINE; PHENYTOIN; TRIFLUOPERAZINE; VALPROIC ACID;

AMINO ACID SUBSTITUTION; ANTICONVULSANT ACTIVITY; ANTICONVULSANT THERAPY; ASIAN; BIPOLAR DISORDER; CAUCASIAN; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG HYDROXYLATION; DRUG MECHANISM; DRUG METABOLISM; DRUG MONITORING; DRUG SAFETY; EPILEPSY; FOCAL EPILEPSY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; GINGIVA HYPERPLASIA; HETEROZYGOTE; HOMOZYGOTE; HUMAN; MONOTHERAPY; PHARMACOGENETICS; PHENOTYPE; PROMOTER REGION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; STEVENS JOHNSON SYNDROME;

ANTICONVULSANTS; ARYL HYDROCARBON HYDROXYLASES; EPILEPSY; GENOTYPE; GLUCURONOSYLTRANSFERASE; HUMANS; PHARMACOGENETICS; PHENYTOIN; POLYMORPHISM, SINGLE NUCLEOTIDE; TRIAZINES;

EID: 79956340310     PISSN: 07925077     EISSN: 07925077     Source Type: Journal    
DOI: 10.1515/DMDI.2011.008     Document Type: Review

References (84)

1. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League against Epilepsy. Epilepsia 1993; 34: 592-6.
2. Hauser WA, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia 2008;49(Suppl 1):8-12.
3. Sander JW, Shorvon SD. Incidence and prevalence studies in epilepsy and their methodological problems: a review. J Neurol Neurosurg Psychiatry 1987;50:829-39. (Pubitemid 17098760)
4. Kotsopoulos IA, van Merode T, Kessels FG, de Krom MC, Knottnerus JA. Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia 2002;43:1402-9. (Pubitemid 35365000)
5. Stephen LJ, Brodie MJ. Selection of antiepileptic drugs in adults. Neurol Clin Epilepsy 2009;27:967-92.
6. Leeman BA, Cole AJ. Advancements in the treatment of epilepsy. Annu Rev Med 2008;59:503-23. (Pubitemid 351287952)
7. Sillanpää M, Schmidt D. Natural history of treated childhood onset epilepsy: prospective, long term population based study. Brain 2006;129:617-24.
8. Basic S, Hajnšek S, Božina N, Filipcic I, Sporiš D, Mišlov D, Posavec A. The influence of C3435T polymorphism of ABCB1 gene on penetration of phenobarbital across the blood-brain barrier in patients with generalized epilepsy. Seizure, 2008;17:524-530.
9. Beghi E. Treating epilepsy across its different stages. Ther Adv Neurol Disord 2010;3:85-92.
10. Holland KD. Efficacy, pharmacology, and adverse effects of antiepileptic drugs. Neurol Clin 2001;19:313-45. (Pubitemid 32531731)
11. Löscher W, Klotz U, Zimprich F, Schmidt D. The clinical impact of pharmacogenetics on the treatment of epilepsy. Epilepsia 2009;50:1-23.
12. Kalow W, Tang BK, Endreyani L. Hypothesis: comparisons of inter-and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics 1998;8:283-9. (Pubitemid 28372321)
13. Anderson GD. Pharmacokinetic, pharmacodynamic, and phar-macogenetic targeted therapy of antiepileptic drugs. Ther Drug Monit 2008;30:173-80. (Pubitemid 351521644)
14. Saruwatari J, Ishitsu T, Nakagawa K. Update on the genetic polymorphisms of drug-metabolizing enzymes in antiepileptic drug therapy. Pharmaceuticals 2010;3:2709-32.
15. McDonagh M, Peterson K, Lee N, Thakurta S. Drug class review: antiepileptic drugs for indications other than epilepsy. Portland, OR: Oregon Health & Science University, 2008.
16. Krasowski MD. Therapeutic drug monitoring of the newer anti-epilepsy medications. Pharmaceuticals (Basel) 2010;3:1909-35.
17. Leach MJ, Marden CM, Miller AA. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia 1986;27:490-7. (Pubitemid 16026042)
18. Cheung H, Kamp D, Harris E. An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res 1992;13:107-12.
19. French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, et al. Efficacy and tolerability of the new antiepi-leptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004;62:1252-60. (Pubitemid 38526035)
20. Beghi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines. Lancet Neurol 2004;3:618-21. (Pubitemid 39221928)
21. Liston HL, Markowitz JS, DeVane CL. Drug glucuronida-tion in clinical psychopharmacology. J Clin Psychopharmacol 2001;21:500-15.
22. Rowland A, Elliot DJ, Williams JA, Mackenzie PI, Dickinson RG, Miners JO. In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug Metab Dispos 2006;34:1055-62. (Pubitemid 43763765)
23. Magdalou J, Herber R, Bidault R, Siest G. In vitro N-glucuronida-tion of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharmacol Exp Ther 1992;260:1166-73.
24. Sánchez M, Herranz JL, Leno C, Arteaga R, Oterino A, Valdizán EM, et al. UGT2B7-161C > T polymorphism is associated with lamotrigine concentration to dose ratio in a multivariate study. Ther Drug Monit 2010;32:177-84.
25. Sánchez MB, Herranz JL, Leno C, Arteaga R, Oterino A, Valdiza EM, et al. Genetic factors associated with drug-resistance of epilepsy: relevance of stratification by patient age and aetiology of epilepsy. Seizure 2010;19:93-101.
26. Wong IC, Lhatoo SD. Adverse reactions to new anticonvulsant drugs. Drug Saf 2000;23:35-56. (Pubitemid 30455916)
27. Llerena A, Dorado P, Peñas-Lledó EM. Pharmacogenetics of de-brisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics 2009;10:17-28.
28. Kirchheiner J, Seeringer A. Clinical implications of pharmacoge-netics of cytochrome P450 drug metabolizing enzymes. Biochim Biophys Acta 2007;1770:489-94. (Pubitemid 46136751)
29. Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Updated September 8, 2008. Accessed 22 February, 2011. Available at: http://www.cypalleles.ki.se/index.html.
30. Yang ZF, Cui HW, Hasi T, Jia SQ, Gong ML, Su XL. Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Mongolian population in China. Genet Mol Res 2010;9: 1844-51.
31. Dorado P, Berecz R, Norberto MJ, Yasar U, Dahl ML, LLerena A. CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers. Eur J Clin Pharmacol 2003;59:221-5. (Pubitemid 37009744)
32. LLerena A, Dorado P, O' Kirwan F, Jepson R, Licinio J, Wong ML. Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards. Pharmacogenomics J 2004;4:403-6. (Pubitemid 39600058)
33. Dorado P, Sosa-Macias MG, Peñas-Lledó EM, Alanis-Bañuelos RE, Wong ML, Licinio J, et al. CYP2C9 allele frequency differences between populations of Mexican-Mestizo, Mexican-Tepehuano, and Spaniards. Pharmacogenomics J 2011;11: 108-112.
34. Taguchi M, Hongou K, Yagi S, Miyawaki T, Takizawa M, Aiba T, et al. Evaluation of phenytoin dosage regimens based on genotyping of CYP2C subfamily in routinely treated Japanese patients. Drug Metab Pharmacokinet 2005;20:107-12.
35. Kubota T, Chiba K, Ishizaki T. Genotyping of S-mephenytoin 4 ′-hydroxylation in an extended Japanese population. Clin Pharmacol Ther 1996;60:661-6. (Pubitemid 27025913)
36. Giancarlo GM, Venkatakrishnan K, Granda BW, von Moltke LL, Greenblatt DJ. Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sul-faphenazole, omeprazole, and ticlopidine. Eur J Clin Pharmacol 2001;57:31-6. (Pubitemid 32391409)
37. Bajpai M, Roskos LK, Shen DD, Levy RH. Roles of cytochrome P450 2C9 and cytochrome P450 2C19 in the stereo selective metabolism of phenytoin to its major metabolite. Drug Metab Dispos 1996;24:1401-3. (Pubitemid 26427180)
38. Hennessy S, Freeman CP, Metlay JP, Chu X, Strom BL, Bilker WB. CYP2C9, CYP2C19, and ABCB1 genotype and hospitaliza-tion for phenytoin toxicity. J Clin Pharmacol 2009;49:1483-7.
39. Hung CC, Lin CJ, Chen CC, Chang CJ, Liou HH. Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther Drug Monit 2004;26:534-40.
40. Ninomiya H, Mamiya K, Matsuo S, Ieiri I, Higuchi S, Tashiro N. Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Ther Drug Monit 2000;22:230-2. (Pubitemid 30196831)
41. Brandolese R, Scordo MG, Spina E, Gusella M, Padrini R. Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin Pharmacol Ther 2001;70:391-4. (Pubitemid 33022480)
42. Lee AY, Kim MJ, Chey W Y, Choi J, Kim BG. Genetic polymorphism of cytochrome P450 2C9 in diphenylhydantoin-induced cutaneous adverse drug reactions. Eur J Clin Pharmacol 2004;60:155-9. (Pubitemid 38757125)
43. Soga Y, Nishimura F, Ohtsuka Y, Araki H, Iwamoto Y, Naruishi H, et al. CYP2C polymorphisms, phenytoin metabolism and gin-gival overgrowth in epileptic subjects. Life Sci 2004;74:827-34. (Pubitemid 37501131)
44. Aynacioglu AS, Brockmoller J, Bauer S, Sachse C, Güzelbey P, Ongen Z, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 1999;48:409-15. (Pubitemid 29417726)
45. Odani A, Hashimoto Y, Otsuki Y, Uwai Y, Hattori H, Furusho K, et al. Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin Pharmacol Ther 1997;62:287-92. (Pubitemid 27417794)
46. Tate SK, Depondt CH, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, et al. Genetic predictors of the maximum doses patients receive during clinical use of the antiepileptic drug carbamazepine and phenytoin. Proc Natl Acad Sci USA 2005;102:5507-12. (Pubitemid 40530288)
47. Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 2006;79:103-13. (Pubitemid 43069582)
48. Klotz U. Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. Int J Clin Pharmacol Ther 2006;44:297-302. (Pubitemid 44043771)
49. Sibbing D, Koch W, Gebhard D, Schuster T, Braun S, Stegherr J, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 2010;121:512-8.
50. Goldstone JV, Hamdoun A, Cole BJ, Howard-Ashby M, Nebert DW, Scally M, et al. The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome. Dev Biol 2006;300:366-84. (Pubitemid 44827001)
51. Dutton GJ, Storey ID. The isolation of a compound of uridine diphosphate and glucuronic acid from liver. Proc Biochem Soc 1953;53:37-8.
52. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, et al. Drug-drug interactions for UDP-Glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCI/AUC) ratios. Drug Metab Dispos 2004;32:1201-8. (Pubitemid 39410902)
53. Ménard V, Girard H, Harvey M, Pérusse L, Guillemette C. Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population. Hum Mutat 2009;30:677-87.
54. Bock KW, Köhle C. Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: advances and open questions. Biochem Pharmacol 2009;77: 1458-65.
55. King C, Rios G, Green M, Tephly T. " UDP- glucuronosyltransferases". Curr Drug Metab 2000;1:143-61.
56. Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 2000;40:581-616. (Pubitemid 30340694)
57. Vore M, Hadd HS, Slikker W Jr. Ethynylestradiol-17 beta D-ring glucuronide conjugates are potent cholestatic agents in the rat. Life Sci 1983;32:2989-93. (Pubitemid 13096624)
58. Shimomura K, Kamata O, Ueki S, Ida S, Oguri K. Analgesic effect of morphine glucuronides. Tohoku J Exp Med 1971;105:45-52.
59. Formelli F, Barua AB, Olson JA. Bioactivities of N-(4-hydroxyphenyl) retinamide and retinoyl beta-glucuronide. FASEB J 1996;10:1014-24. (Pubitemid 26285977)
60. Hahn KK, Wolff JJ, Kolesar JM. Pharmacogenetics and irinote-can therapy. Am J Health Syst Pharm 2006;63:2211-7.
61. Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Bélanger A, et al. The UDP glycosyltransferase gene superfam-ily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 1997;7:255-69. (Pubitemid 27358064)
62. Burchell B, Brierley CH, Monaghan G, Clarke DJ. The structure and function of the UDP-glucuronosyltransferase gene family. Adv Pharmacol 1998;42:335-8.
63. Iyanagi T, Watanabe T, Uchiyama Y. The 3-methylcholanthrene-inducible UDP-glucuronosyltransferase deficiency in the hyper-bilirubinemic rat (Gunn rat) is caused by a-1 frameshift mutation. J Biol Chem 1989;264:21302-7. (Pubitemid 20017951)
64. Iyanagi T. Molecular basis of multiple UDP-glucuronosyl-transferase isoenzyme deficiencies in the hyperbilirubinemic rat (Gunn rat). J Biol Chem 1991;266:24048-52. (Pubitemid 21908903)
65. Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, et al. A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem 1992;267:3257-61.
66. Li Q, Lamb G, Tukey RH. Characterization of the UDP- glucuronosyltransferase 1A locus in lagomorphs: evidence for duplication of the UGT1A6 gene. Mol Pharmacol 2000;58:89-97. (Pubitemid 30452531)
67. Harding D, Jeremiah SJ, Povey S, Burchell B. Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1. Ann Hum Genet 1990;54:17-21. (Pubitemid 20035019)
68. Zhang T, Haws P, Wu Q. Multiple variable first exons: a mechanism for cell-and tissue-specific gene regulation. Genome Res 2004;14:79-89. (Pubitemid 38088528)
69. Strassburg CP, Kneip S, Topp J, Oberer-Straub P, Barut A, Tukey RH, et al. Polymorphic gene regulation and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine. J Biol Chem 2000;275:36164-71.
70. Starlard-Davenport A, Lyn-Cook B, Beland FA, Pogribny IP. The role of UDP-glucuronosyltransferases and drug transporters in breast cancer drug resistance. Exp Oncol 2010;32:172-80.
71. Wiener D, Fang JL, Dossett N, Lazarus P. Correlation between UDP-glucuronosyltransferase genotypes and 4-(methylnitro-samino)-1-(3-pyridyl)- 1-butanone glucuronidation phenotype in human liver microsomes. Cancer Res 2004;64:1190-6. (Pubitemid 38176928)
72. Ehmer U, Vogel A, Schütte JK, Krone B, Manns MP, Strassburg CP. Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4. Hepatology 2004;39:970-7. (Pubitemid 38428936)
73. Saeki M, Saito Y, Jinno H, Sai K, Hachisuka A, Kaniwa N, et al. Genetic variations and haplotypes of UGT1A4 in a Japanese population. Drug Metab Pharmacokinet 2005;20:144-51.
74. Mori A, Maruo Y, Iwai M, Sato H, Takeuchi Y. UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation. Drug Metab Dispos 2005;33:672-5. (Pubitemid 40593882)
75. Kim DW, Kim M, Lee SK, Kang R, Lee SY. Lack of association between L48V polymorphism in the UGT1A4 gene and lamotrigine-induced rash. J Korean Epilepsy Soc 2006;10:31-4.
76. Benoit-Biancamano MO, Adam JP, Bernard O, Court MH, Leblanc MH, Caron P, et al. A pharmacogenetics study of the human glucuronosyltransferase UGT1A4. Pharmacogenet Genomics 2009;19:945-54.
77. UGT Alleles Nomenclature Home Page. UGT Nomenclature Committee. June 2005. Accessed 22 February, 2011. Available at: http://www.ugtalleles.ulaval.ca.
78. Court MH. Interindividual variability in hepatic drug glucuroni-dation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system. Drug Metab Rev 2010;42:202-17.
79. Glubb DM, Innocenti F. Mechanisms of genetic regulation in gene expression: examples from drug metabolizing enzymes and transporters. Wiley Interdiscip Rev Syst Biol Med 2011;3:299-313.
80. Guillemette C. Pharmacogenomics of human UDP glucuronosyl-transferase. Pharmacogenomics J 2003;3:136-58.
81. Bhasker CR, McKinnon W, Stone A, Lo AC, Kubota T, Ishizaki T, et al. Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance. Pharmacogenetics 2000;10:679-85.
82. Saeki M, Saito Y, Jinno H, Tanaka-Kagawa T, Ohno A, Ozawa S, et al. Single nucleotide polymorphisms and haplotype frequencies of UGT2B4 and UGT2B7 in a Japanese population. Drug Metab Dispos 2004;32:1048-54. (Pubitemid 39096067)
83. Hines RN, Koukouritaki SB, Poch MT, Stephens MC. Regulatory polymorphisms and their contribution to interindividual differences in the expression of enzymes influencing drug and toxicant disposition. Drug Metab Rev 2008;40:263-301. (Pubitemid 352000944)
84. Guillemette C, Levesque E, Harvey M, Bellemare J, Menard V. UGT genomic diversity: beyond gene duplication. Drug Metab Rev 2010;42:22-42.