JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2011, 60(4):165-170

Clinical significance of cytochrome P450 genetic polymorphism - part II. Cytochrome P450 2C9

Jana Ďuricová*, Milan Grundmann
Ostravska Univerzita v Ostravě, Ustav klinicke farmakologie LF OU a FN

Cytochrome P450 2C9 is the major enzyme of the cytochrome P450 2C subfamily and metabolizes approximately 10 % of commonly used drugs. Several studies have demonstrated that the CYP2C9 polymorphism is important for several drugs and may be associated with the occurrence of clinically relevant side effects. Part II of this paper focuses on the influence of genetic polymorphism of cytochrome P450 2C9 on drug effect.

Keywords: cytochrome P450; genetic polymorphism; CYP2C9

Received: January 31, 2011; Accepted: April 11, 2011; Published: April 1, 2011  Show citation

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Ďuricová J, Grundmann M. Clinical significance of cytochrome P450 genetic polymorphism - part II. Cytochrome P450 2C9. Čes. slov. farm. 2011;60(4):165-170.
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    References

    1. Goldstein, J. A.: Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br. J. Clin. Pharmacol. 2001; 52, 349-355. Go to original source... Go to PubMed...
    2. Miners, J. O., Birkett, D. J.: Cytochrome P450 2C9: an enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol. 1998; 45, 525-538. Go to original source... Go to PubMed...
    3. Kirchheiner, J., Tsahuridu, M., Jabrane, W., Roots, I., Brockmöller, J.: The CYP2C9 polymorphism: from enzyme kinetics to clinical dose recommendations. Personalized Med. 2004; 1, 63-84. Go to original source... Go to PubMed...
    4. Schwarz, U. I.: Clinical relevance of genetic polymorphisms in the human CYP2C9. Eur. J. Clin. Invest. 2003; 33, 23-30. Go to original source... Go to PubMed...
    5. García-Martín, E., Martínez, C., Ladero, J. M., Agúndez, J. A.: Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals. Mol. Diag. Ther. 2006; 10, 29-40. Go to original source... Go to PubMed...
    6. Rettie, A. E., Jones, J. P.: Clinical and toxicological relevance of CYP2C9: Drug-drug interactions and pharmacogenetics. Annu. Rev. Pharmacol. Toxicol. 2005; 45, 477-494. Go to original source... Go to PubMed...
    7. Aithal, G. P., Day, C.P., Kesteven, P. J., Daly, A. K.: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353, 717-719. Go to original source... Go to PubMed...
    8. Linder, M. W., Looney, S., Adams, J. E., Johnson, N., Antonino-Green, D., Lacefield, N., Bukaveckas, B. L., Valdes R.: Warfarin dose adjustments based on CYP2C9 genetic polymorphisms. J. Thromb. Thrombolysis. 2002; 14, 227-232. Go to original source... Go to PubMed...
    9. Scordo, M. G., Pengo, V., Spina, E., Dahl, M. L., Gusella, M., Padrini, R.: Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin. Pharmacol. Ther. 2002; 72, 702-710. Go to original source... Go to PubMed...
    10. Peyvandi, F., Spreafico, M., Siboni, S. M., Moia, M., Mannucci, P. M.: CYP2C9 genotypes and dose requirements during the induction phase of oral anticoagulant therapy. Clin. Pharmacol. Ther. 2004; 75, 198-203. Go to original source... Go to PubMed...
    11. Higashi, M. K., Veenstra, D. L., Kondo, L. M, Wittkowsky, A. K., Srinouanprachanh, S. L., Farin, F. M., Rettie, A. E.: Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002; 287, 1690-1698. Go to original source... Go to PubMed...
    12. Sanderson, S., Emery, J., Higgins, J.: CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. Genet. Med. 2005; 7, 97-104. Go to original source... Go to PubMed...
    13. Sconce, E. A., Khan, T. I., Wynne, H. A., Avery, P., Monkhouse, L., King, B. P., Wood, P., Kesteven, P., Daly, A. K., Kamali, F.: The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 2005; 106, 2329-2333. Go to original source... Go to PubMed...
    14. Caldwell, M. D., Berg, R. L., Zhang, K. Q., Glurich, I., Schmelzer, J. R., Yale, S. H., Vidaillet, H. J., Burmester, J. K.: Evaluation of genetic factors for warfarin dose prediction. Clin. Med. Res. 2006; 5, 8-16. Go to original source... Go to PubMed...
    15. Wadelius M., Chen L. Y., Lindh J. D., Eriksson, N., Ghori, M. J., Bumpstead, S., Holm, L., McGinnis, R., Rane, A., Deloukas, P.: The largest prospective warfarin-treated cohort supports genetic forecasting. Blood. 2009; 113, 784-792. Go to original source... Go to PubMed...
    16. Ferder, N. S., Eby, C. S., Deych, E., Harris, J. K., Ridker, P. M. Milligan, P. E., Goldhaber, S. Z., King, C. R., Giri, T., McLeod, H. L., Glynn, R. J., Gage, B. F.: Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy. J. Thromb. Haemost. 2010; 8, 95-100. Go to original source... Go to PubMed...
    17. Roper, N., Storer, B., Bona, R., Fang, M.: Validation and comparison of pharmacogenetics-based warfarin dosing algorithms for application of pharmacogenetic testing. J. Mol. Diagn. 2010; 12, 283-291. Go to original source... Go to PubMed...
    18. van Schie, R. M., Wadelius, M. I., Kamali, F., Daly, A. K., Manolopoulos, V. G., de Boer, A., Verhoef, T. I., Kirchheiner, J., Haschke-Becher, E., Briz, M., Rosendaal, F. R., Redekop, W. K., Pirmohamed, M., Maitland van der Zee A. H.: Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design. Pharmacogenomics 2009; 10, 1687-1695. Go to original source... Go to PubMed...
    19. Shon, J. H., Yoon, Y. R., Kim, K. A., Lim, Y. C., Lee, K. J., Park, J. Y., Cha, I. J., Flockhart, D. A., Shin, J. G.: Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans. Pharmacogenetics 2002; 12, 111-119. Go to original source... Go to PubMed...
    20. Yin, O. Q., Tomlinson, B., Chow, M. S.: CYP2C9, but not CYP2C19, polymorphisms affect the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. Clin. Pharmacol. Ther. 2005; 78, 370-377. Go to original source... Go to PubMed...
    21. Kirchheiner, J., Brockmöller, J., Meineke, I., Bauer, S., Rohde, W., Meisel, C., Roots, I.: Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin. Pharmacol. Ther. 2002; 71, 286-296. Go to original source... Go to PubMed...
    22. Niemi, M., Cascorbi, I., Timm, R., Kroemer, H. K., Neuvonen, P. J., Kivistö, K. T.: Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin. Pharmacol. Ther. 2002; 72, 32-332. Go to original source... Go to PubMed...
    23. Kirchheiner, J., Bauer, S., Meineke, I., Rohde, W., Prang, V., Meisel, C., Roots, I., Brockmöller, J.: Impact of CYP2C9 and CYP2C19 polymorphisms on tolbutamide kinetics and the insulin and glucose response in helathy volunteers. Pharmacogenetics 2002; 12, 101-109. Go to original source... Go to PubMed...
    24. Kirchheiner, J., Roots, I., Goldammer, M., Rosenkranz, B., Brockmöller, J.: Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance. Clin. Pharmacokinet. 2005; 44, 1209-1225. Go to original source... Go to PubMed...
    25. Suzuki, K., Yanagawa, T., Shibasaki, T., Kaniwa, N., Hasegawa, R., Tohkin, M.: Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepirid in subjects with type 2 diabetes. Diabetes Res. Clin. Pract. 2006; 72, 148-154. Go to original source... Go to PubMed...
    26. Becker, M. L., Visser, L. E., Trienekens, P. H., Hofman, A., van Schaik, R. H., Stricker, B. H.: Cytochrome P450 2C9*2 and *3 polymorphisms and the dose and effect of sulfonylurea in type II diabetes mellitus. Clin. Pharmacol. Ther. 2008; 83, 288-292. Go to original source... Go to PubMed...
    27. Holstein A., Plaschke A., Ptak M., Egberts, E. H., El-Din, J., Brockmöller, J., Kirchheiner, J.: Association between CYP2C9 slow mwtabolizer gynotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents. Br. J. Clin. Pharmacol. 2005; 60, 103-106. Go to original source... Go to PubMed...
    28. Ragia, G., Petridis, I., Tavridou, A., Christakidis, D., Manolopoulous, V. G.: Presence of CYP2C9*3 allele increases risk for hypoglycemia in Type 2 diabetic patients treated with sulfonylureas. Pharmacogenomics 2009; 10, 1781-1787. Go to original source... Go to PubMed...
    29. Kirchheiner J., Meineke I., Müller G., Bauer, S., Rohde, W., Meisel, C., Roots, I., Brockmöller, J.: Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin. Pharmacokinet. 2004; 43, 267-278. Go to original source... Go to PubMed...
    30. Yasar, U., Forslund-Bergengren, C., Tybring, G., Dorado, P., Llerena, A., Sjöqvist, F., Eliasson, E., Dahl, M. L.: Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin. Pharmacol. Ther. 2002; 71, 89-98. Go to original source... Go to PubMed...
    31. Sekino, K., Kubota, T., Okada, Y., Yamada, Y., Yamamoto, K., Horiuchi, R., Kimura, K., Iga, T.: Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects. Eur. J. Clin. Pharmacol. 2003; 59, 589-592. Go to original source... Go to PubMed...
    32. Lajer, M., Tarnow, S., Andersen, S., Parving, H. H.: CYP2C9 variant modifies blood pressure-lowering response to losartan in Type 1 diabetic patients with nephropathy. Diabet. Med. 2007; 24, 322-328. Go to original source... Go to PubMed...
    33. Joy, M. S., Dornbrook-Lavender, K., Blaisdell, J., Hilliard, T., Boyette, T., Hu, Y., Hogan, S. L., Candiani, C., Falk, R. J., Goldstein, J. A.: CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases. Eur. J. Clin. Pharmacol. 2009; 65, 947-953. Go to original source... Go to PubMed...
    34. Lee, C. R., Pieper, J. A., Hinderliter, A. L., Blaisdell, J. A., Goldstein, J. A.: Losartan and E3174 pharmacokinetics in cytochrome P450 2C9*1/*1, *1/*2, and *1/*3 individuals. Pharmacotherapy 2003; 23, 720-725. Go to original source... Go to PubMed...
    35. Donner, K. M., Hiltunen, T. P., Suonsyrjä, T., Hannila-Handelberg, T., Tikkanen, I., Antikainen, M., Hirvonen, A., Kontula, K.: CYP2C9 genotype modifies activity of the renin-angiotensin-aldosterone system in hypertensive men. J. Hypertens. 2009; 27, 2001-2009. Go to original source... Go to PubMed...
    36. Chen, G., Jiang, S., Mao, G., Zhang, S., Hong, X., Tang, G., Li, Z., Liu, X., Zhang, Y., Xing, H., Wang, B., Yu, Y, Xu, X.: CYP2C9 Ile359Leu polymorphism, plasma irbesartan concentration and acute blood pressure reductions in response to irbesartan treatment in Chinese hypertensive patients. Methods. Find. Exp. Clin. Pharmacol. 2006; 28, 19-24. Go to original source... Go to PubMed...
    37. Hallberg, P., Karlsson, J., Kurland, L., Lind, L., Kahan, T., Malmqvist, K., Ohman, K. P., Nyström, F., Melhus, H.: The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. J. Hypertens. 2002; 20, 2089-2093. Go to original source... Go to PubMed...
    38. Hong, X., Zhang, S., Mao, G., Jiang, S., Zhang, Y., Yu, Y., Tang, G., Xing, H., Xu, X.: CYP2C9*3 allelic variant is associated with netabolism of irbesartan in Chinese population. Eur. J. Clin. Pharmacol. 2005; 61, 627-634. Go to original source... Go to PubMed...
    39. Blanco, G., Martínez, C., García-Martín, E., Agúndez, J. A.: Cytochrome P450 gene polymorphisms and variability in response to NSAIDS. Clin. Res. Reg. Affairs 2005; 22, 57-81. Go to original source...
    40. Kirchheiner, J., Störmer, E., Meisel, C., Steinbach, N., Roots, I., Brockmöller, J.: Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics 2003; 13, 473-480. Go to original source... Go to PubMed...
    41. Lundblad, M. S., Ohlsson, S., Johansson, P., Lafolie, P., Eliasson, E.: Accumulation of celekoxib with a 7-fold higher drug exposure in individuals homozygous for CYP2C9*3. Clin. Pharmacol. Ther. 2006; 79, 287-288. Go to original source... Go to PubMed...
    42. López-Rodríguez, R., Novalbos, J., Gallego-Sandín, S., Román-Martínez, M., Torrado, J., Gisbert, J. P., Abad-Santos, F.: Influence of CYP2C8 and CYP2C9 polymorphisms on pharmacokinetic and pharmacodynamic parameters of racemic and enantiomeric forms of ibuprofen in healthy volunteers. Pharmacol. Res. 2008; 58, 77-84. Go to original source... Go to PubMed...
    43. García-Martín, E., Martínez, C., Tabarés, B., Frías, J., Agúndez, J. A.: Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin. Pharmacol. Ther. 2004; 76, 119-127. Go to original source... Go to PubMed...
    44. Kirchheiner, J., Meineke, I., Freytag, G., Meisel, C., Roots, I., Brockmöller, J.: Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenase 1 and 2. Clin. Pharmacol. Ther. 2002; 72, 62-75. Go to original source... Go to PubMed...
    45. Samowitz, W. S., Wolff, R. K., Curtin, K., Sweeney, C., Ma, K. N., Andersen, K., Levin, T. R., Slattery, M. L.: Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal prevention. Clin. Gastroenterol. Hepatol. 2006; 4, 894-901. Go to original source... Go to PubMed...
    46. Zhang, Y., Zhong, D., Si, D., Guo, Y., Chen, X., Zhou, H.: Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype. Br. J. Clin. Pharmacol. 2005; 59, 14-17. Go to original source... Go to PubMed...
    47. Vianna-Jorge, R., Perini, J. A., Rondinelli, E., Suarez-Kurtz, G.: CYP2C9 genotypes and pharmacokinetics of tenoxicam in Brazilians. Clin. Pharmacol. Ther. 2004; 76, 18-26. Go to original source... Go to PubMed...
    48. Perini, J. A., Vianna-Jorge, R., Brogliato, A. R., Suarez-Kurtz, G.: Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. Clin. Pharmacol. Ther. 2005; 78, 362-369. Go to original source... Go to PubMed...
    49. Shimamoto, J., Ieiri, I., Urae, A., Kimura, M., Irie, S., Kubota, T., Chiba, K., Ishizaki, T., Otsubo, K., Higuchi, S.: Lack of differences in diclofenac (a substrate for CYP2C9) pharmacokinetics in healthy volunteers with respect to the single CYP2C9*3 allele. Eur. J. Clin. Pharmacol. 2000; 56, 65-68. Go to original source... Go to PubMed...
    50. Yasar, Ü., Eliasson, E., Forslund-Bergengren, C., Tybring, G., Gadd, M., Sjöqvist, F., Dahl, M. L.: The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro. Eur. J. Clin. Pharmacol. 2001; 57, 729-735. Go to original source... Go to PubMed...
    51. Martin, J. H., Begg, E. J., Kennedy, M. A., Roberts, R., Barclay, M. L.: Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration? Br. J. Clin. Pharmacol. 2001; 51, 627-630. Go to original source... Go to PubMed...
    52. Martínez, C., Blanco, G., Ladero, J. M., García-Martín, E., Taxonera, C., Gamito, F. G., Diaz-Rubio, M., Agúndez, J. A.: Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br. J. Pharmacol. 2004; 141, 205-208. Go to original source... Go to PubMed...
    53. Scarcelli, C., Colaizzo, D., Grandone, E., Nir,o V., Andriulli, A., Leandro, G., Di Mario, F., Dallapiccola, B.: Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastronenterology 2007; 133, 465-471. Go to original source... Go to PubMed...
    54. Carbonell, N., Verstuyft, C., Massard, J., Letierce, A., Cellier, C., Deforges, L., Saliba, F., Delchier, J. C., Becquemont, L.: CYP2C9*3 loss-of-function allele is associated with acute upper gastrointestinal bleeding related to the use of NSAIDs other than aspirin. Clin. Pharmacol. Ther. 2010; 87, 693-698. Go to original source... Go to PubMed...
    55. Tassaneeyakul, W., Veronese, M. E., Birkett, D. J., Doecke, C. J., McManus, M. E., Sansom, L. N., Miners, J. O.: Co-regulation of phenytoin and tolbutamide metabolism in humans. Br. J. Clin. Pharmac. 1992; 34, 494-498.
    56. Taguchi, M., Hongou, K., Yagi, S., Miyawaki, T., Takizawa, M., Aiba, T., Hashimoto, Y.: Evaluation of phenytoin dosage regimens based on genotyping of CYP2C subfamily in routinely treated Japanese patients. Drug. Metab. Pharmacokinet. 2005; 20, 107-112. Go to original source... Go to PubMed...
    57. Kerb, R., Aynacioglu, A. S., Brockmöller, J., Schlagenhaufer, R., Bauer, S., Szekeres, T., Hamwi, A., Fritzer-Szekeres, M., Baumgartner, C., Ongen, H. Z., Güzelbey, P., Roots, I., Brinkmann, U.: The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels. Pharmacogenomics 2001; 1, 204-210. Go to original source... Go to PubMed...
    58. Lee, S. Y., Lee, S. T., Kim, J. W.: Contributions of CYP2C9/CYP2C19 genotypes and drug interaction to the phenytoin treatment in the Korean epileptic patients in the clinical setting. J. Biochem. Mol. Biol. 2007; 40, 448-452. Go to original source... Go to PubMed...
    59. Aynacioglu, A. S., Brockmöller, J., Bauer, S., Sachse, C., Güzelbey, P., Ongen, Z., Nacak, M., Roots, I.: Frequency of cytochrome P4502C9 variants in a Turkish population and functional relevance for phenytoin. Br. J. Clin. Pharmacol. 1999; 48: 409-415. Go to original source... Go to PubMed...
    60. Tate, S. K., Depondt, C., Sisodiya, S. M., Cavalleri, G. L., Schorge, S., Soranzo, N., Thom, M., Sen, A., Shorvon, S. D., Sander, J. W., Wood, N. W., Goldstein, D. B.: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc. Natl. Acad. Sci. 2005; 102, 5507-5512. Go to original source... Go to PubMed...
    61. van der Weide, J., Steijns, L. S., van Weelden, M. J., de Haan, K.: The effect of genetic polymorphisms of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 2001; 11, 287-291. Go to original source... Go to PubMed...
    62. Kesavan, R., Narayan, S. K., Adithan, C.: Influence of CYP2C9 and Cyp2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients. Eur. J. Clin. Pharmacol. 2010; 66, 689-696. Go to original source... Go to PubMed...
    63. Ninomiya, H., Mamiya, K., Matsuo, S., Leiri, 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, 230-232. Go to original source... Go to PubMed...
    64. Kidd, R. S., Curry, T. B., Gallagher, S., Edeki, T., Blaisdell, J., Goldstein, J. A.: Identification of a null allele of CYP2C9 in an African-american exhibiting toxicity to phenytoin. Pharmacogenetics 2001; 11, 803-808. Go to original source... Go to PubMed...
    65. Brandolese, R., Scordo, M. G., Spina, E., Gusella, M., Padrini, R.: Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin. Pharmacol. Ther. 2001; 70, 391-394. Go to original source...
    66. McCluggage, L. K., Voils, S. A., Bullock, M. R.: Phenytoin toxicity due to genetic polymorphism. Neurocrit. Care 2009; 10, 222-224. Go to original source... Go to PubMed...
    67. Soga, Y., Nishimura, F., Ohtsuka, Y., Araki, H., Iwamoto, Y., Naruishi, H., Shiomi, N., Kobayashi, Y., Takashiba, S., Shimizu, K., Gomita, Y., Oka, E.: CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects. Life Sci. 2004; 74, 827-834. Go to original source... Go to PubMed...
    68. Lee, A. Y., Kim, M. J., Chey, W. Y., Choi, J., Kim, B. G.: Genetic polymorphism of cytochrome P450 2C9 in diphenylhydantoin-induced cutaneous adverse drug reactions. Eur. J. Clin. Pharmacol. 2004; 60, 155-159. Go to original source... Go to PubMed...
    69. P450 Drug Interaction Table. http://medicine.iupui.edu/clinpharm/ddis/table.aspx (17. 5. 2011).
    70. Suchopár, J., Buršík, J., Mach, R., Prokeš, M.: Kompendium lékových interakcí. 1. vyd. InfoPharm 2005.
    71. Baxter, K., Davis, M., Driver, S. (eds.): Stockley's drug interactions, 8th ed. Suffolk: Pharmaceuticals Press, 2008.

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