CYP2C9 polymorphisms

Lastly, Llerena etal. (2004) compared the CYP2C9 polymorphisms 1, 2, 3, 4, 5, and 6 in Mexican Americans (n = 98) and Spanish subjects (n = 102). Lower frequencies of the variant CYP2C9 2, one of two alleles reported to have altered catalytic activity, were found among the Mexican Americans. Since no phenotypic comparisons were conducted in this study, the clinical implications remain unclear. The authors suggest the need for further studies to assess whether the drug metabolism of medications such as warfarin maybe affected in this population. 

Taube J, Halsall D, Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000 ... 

Taube, et al., "Influence of Cytochrome P-450 CYP2C9 Polymorphisms on Warfarin Sensitivity and Risk of Over-Anticoagulation in Patients on Long-Term Treatment," Blood, 96,1816-1819 (2000). 

Kirchheiner J, Ufer M, Walter E, et al. Effects of CYP2C9 polymorphisms on the pharmacokinetics of R- and S-phenprocoumon in healthy volunteers. Pharmacogenetics 2004 14 19-26. 

While data have been available for some time in relation to maintenance dose (24), the effect of CYP2C9 polymorphisms on dose requirements during the induction phase (25), when the danger of bleeding complications likely is greatest, has also been studied patients with 2C9 2 or 2C9 3 variant alleles more frequently had INR values above the upper limit of the target range (3.0) (65% for 2C9 2/- and 66% for 2C9 3/- Vs. 33% for 2Cp l/l p = 0.006 and. 012, respectively). 

Kirchheiner J, Kudlicz D, Meisel C, et al. Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (—)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clin Pharmacol Ther 2003 74(2) 186-194. 

King, B.P. et al. Upstream and coding region CYP2C9 polymorphisms correlation with warfarin dose and metabolism. Pharmacogenetics 2004, 14 813-822. 

Further in vitro/in vivo investigations are needed to assess the relationship between CYP2C8 (and CYP2C9) polymorphisms and drag metabolic clearance, in order to address the clinical relevance of CYP2C8 genotyping. 

A CYP2C9 polymorphism has been implicated in the pathogenesis of leflunomide hepatotoxicity (77). 

Herman D, Locatelli I, Grabnar I, et al. Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose. Pharmacogenomics J 2005 5(3) 193-202. 

Chern HD, Ueng TH, Fu YP, et al. CYP2C9 polymorphism and warfarin sensitivity in Taiwan Chinese. Clin Chim Acta 2006 367(l—2) 108—13. 

Miners, J. (2002). CYP2C9 polymorphism Impact on tolbutamide pharmacokinetics and response. Pharmacogenetics 12, 91-92. 

Daly AK, Day CP, Aithal GP. CYP2C9 polymorphism and warfarin dose requirements. Br J Clin Pharmacol 2002 53 408-409. 

Malhi H, Atac B, Daly AK, Gupta S. Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication. Postgrad Med J... 

R. Chen, H. Ho, C. Yu, M. Sheu, Development of swelUng/floating gastroretentive drug delivery system based on a combination of hy-droxyethyl cellulose and sodium carboxymethyl cellulose for losar-tan and its clinical relevance in healthy volunteers with CYP2C9 polymorphism. Fur. J. Pharm. Sci. 39 (1) (2010) 82-89. 

Susceptibility factors Genetic A valproate metabolite, 4-ene-valproate, whose formation is catalyzed by cytochrome CYP2C9, has been reported to contribute to hepatotox-icity caused by valproate. The correlation between CYP2C9 polymorphisms and the concentration of 4-ene-valproate has been studied using blood samples from 68 patients taking valproate and 50 healthy volunteers [343 ]. Mutated alleles had no significant effect on 4-ene-valproate production. No patient had a toxic concentration of 4-ene-valproate or saturation of beta-oxidation. 

Amini-Shirazi N, Ghahremani MH, Ahmadkhaniha R, Mandegary A, Dadgar A, Abdollahi M, Shadnia S, Pakdaman H, Kebriaeezadeh A. Influence of CYP2C9 polymorphism on metabohsm of valproate and its hepatotoxin metabolite in Iranian patients. Toxicol Mech Methods 2010 20(8) 452-7. 

Goldstein JA, Blaisdell JA, Limdi NA. A potentially deleterious new CYP2C9 polymorphism identified in an African American patient with major hemorrhage on warfarin therapy. Blood Cells Mol Dis 2009 42(2) 155-8. 

CYP2C9 polymorphisms have also been associated with a significant reduction in cerebellar white matter volume, but not in total cerebellar volume, in patients taking phenytoin... 

Twardowschy CA, Werneck LC, Scola RH, Borgio JG, De Paola L, Silvado C. The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy. Seizure April 2013 22(3) 194r-7. 

Phabphal K, Geater A, Limapichart K, Sathirapanya P, Setthawatcharawanich S. Role of CYP2C9 polymorphism in phenytoin-related metabolic abnormalities and subclinical atherosclerosis in young adult epileptic patients. Seizure 2013 22 103-8. 

Thakkar AN, Bendkhale SR, Taur SR, Gogtay NJ, Thatte UM. Association of CYP2C9 polymorphisms with phenytoin toxicity in Indian patients. Neurol India 2012 60 577-80. 

Lund K, Gaffney D, Spooner R, Etherington AM, Tansey P, Tail RC. Polymorphisms in VKORCl have more impact than CYP2C9 polymorphisms on early warfarin International Normalized Ratio control and bleeding rates. Br J Haematol 2012 158(2) 256-61. 

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