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Dragana Dragas Milovanovic, Ivan Radosavljevic, Marija Radovanovic, Jasmina R. Milovanovic, Slobodan Obradovic, Slobodan Jankovic, Dragan Milovanovic and Natasa Djordjevic

2008; 30(9):707-13. 9. Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10,11-epoxide formation. Biochem Pharmacol 1994; 47(11):1969-79. 10. Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics 2013; 138:103-41. 11. Lee SJ, Usmani KA, Chanas B, et al. Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups

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Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai and Supeecha Wittayalertpanya

individualized dosage is required to achieve optimum C 0 levels. A major factor affecting dosage variations is genetic polymorphisms of the cytochrome P450 (CYP) enzymes. CYP3A5 is a major isoform responsible for the metabolism of tacrolimus. Many reports have indicated that the interindividual variations seen in pharmacokinetics of tacrolimus were from CYP3A5 single nucleotide polymorphism [ 4 , 5 , 6 , 7 ]. CYP3A5 accounts for approximately 10% of CYP enzymes in the liver. It is also expressed in extrahepatic tissues, such as kidneys, lungs, and prostate glands [ 8 ]. A

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Valon Krasniqi, Aleksandar Dimovski, Hasime Qorraj Bytyqi, Aleksandar Eftimov, Livija Šimičević and Nada Božina

Italian population. Pharmacol Res 2004;50:195-200. doi: 10.1016/j.phrs.2004.01.004 11. Scott SA, Sangkuhl K, Shuldiner AR, Hulot JS, Thorn CF, Altman RB, Klein TE. PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenet Genomics 2012;22:159-65. doi: 10.1097/FPC.0b013e32834d4962 12. Lamba J, Hebert JM, Schuetz EG, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics 2012;22:555-8. doi: 10.1097/FPC.0b

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Nikola Z. Stefanović, Tatjana P. Cvetković, Radmila M. Veličković-Radovanović, Tatjana M. Jevtović-Stoimenov, Predrag M. Vlahović, Ivana R. Stojanović and Dušica D. Pavlović

transplant recipients on triple immunosuppressive therapy. Basic Clin Pharmacol Toxicol 2010; 106: 505–10. 4. Staatz CE, Goodman LK, Tett SE. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Clin Pharmacokinet 2010; 49: 141–75. 5. Novaković I, Maksimović N, Pavlović A, Žarković M, Rovčanin B, Mirković D, Pekmezović T. Cvetković D. Introduction to molecular genetic diagnostics. J. Med Biochem 2014; 33: 3–7. 6. Marchewka Z, Kuźniar J, Zynek-Litwin M, Falkiewicz K

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Lucie Bořek-Dohalská, Petr Hodek, Jiří Hudeček and Marie Stiborová

-80. Koley, A. P., J. T. Buters, R. C. Robinson, A. Markowitz, and F. K. Friedman. (1997) Differential mechanisms of cytochrome P450 inhibition and activation by alpha-naphthoflavone. J Biol Chem   272 : 3149-52. Kumar, S., D. R. Davydov, and J. R. Halpert. (2005) Role of cytochrome B5 in modulating peroxide-supported cyp3a4 activity: evidence for a conformational transition and cytochrome P450 heterogeneity. Drug Metab Dispos   33 : 1131-6. Omura, T., and R. Sato. (1964) The Carbon Monoxide-Binding Pigment of Liver

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Nada Božina, Vlasta Bradamante and Mila Lovrić

, Plowchalk DR, Cook J, Guo F, Obach RS. Application of CYP3A4 in vitro data to predict clinical drug-drug interactions; predictions of compounds as objects of interaction. Br J Clin Pharmacol 2008;65:680--92. Diaz DS, Kozar MP, Smith KS, Asher CO, Sousa JC, Schiehser GA, Jacobus DP, Milhous WK, Skillman DR, Shearer TW. Role of specific cytochrome P450 isoforms in the conversion of phenoxypropoxybiguanide analogs in human liver microsomes to potent antimalarial dihydrotriazines. Drug Metab Dispos 2008;36:380--5. Lobo

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DD Milovanovic, JR Milovanovic, M Radovanovic, I Radosavljevic, S Obradovic, S Jankovic, D Milovanovic and N Djordjevic

steady-state carbamazepine serum concentrations were determined by validated high pressure liquid chromatography (HPLC) assay, as described by Jankovic et al . [ 10 ]. An additional blood sample was taken for CYP2C8 genotyping, and DNA was isolated using the Pure-linkTM genomic DNA kit (Invitrogen, Carlsbad, CA, USA). CYP2C8*3 (416G>A, rs11572080) and CYP2C8*5 (475delA, rs72558196) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific (AS)-PCR methods, respectively, according to Nakajima et al

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Wanwisa Maneechay, Voravit Chittithavorn, Laorrat Lertlam, Thassanan Sirisathienrooch, Pongsanae Duangpakdee and Surasak Sangkhathat

maintenance dosages. For CYP2C9 , the genotype frequency of heterozygous AC ( CYP2C9 * 1 * 3 ) in the rs1958910 was 17/210 or 8.1%. The genotype distribution of VKORCI (rs9923231) in the 210 controls was 118:72:20 individuals or 56.2%:34.3%:9.5% for AA:AG:GG. Genotype distributions of the 3 SNPs in the cases studied and association between warfarin dose and genotypes of rs1059810 and rs9923231 A total of 166 patients receiving warfarin during the period of study were eligible to participate in the study. Of the 12 excluded cases, 11 were excluded because the target

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Kapedanovska A. Nestorovska, K. Jakovski, Z. Naumovska, Hiljadnikova M. Bajro, Z. Sterjev, A. Eftimov, Matevska N. Geskovska, L. Suturkova, K. Dimitrovski, N. Labacevski and A. J. Dimovski

of genetic diversity and signals of natural selection for human ADME genes. Hum Mol Genet. 2011; 20(3): 528-540. 5. Sistonen J, Fuselli S, Palo JU, Chauhan N, Padh H, Sajantila A. Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scale. Pharmacogenet Genomics. 2009; 19(2): 170-179. 6. Yang X, Zhang B, Molony C, Chudin E, Hao K, Zhu J, et al. Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. Genome Res. 2010; 20(8): 1020-1036. 7. McGraw J

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Vessela Vitcheva, Magdalena Kondeva-Burdina and Mitka Mitcheva

affecting metabolism and disposition — Enzyme inhibition. In: Principles of Biochemical Toxicology. 3 rd ed. New York (NY): Taylor and Francis; 2000. p. 164-5. Graham RJ, Benet LZ. Antiprogestin-mediated inactivation of cytochrome P 450 CYP 3A4. Int J Exp Clin Pharmacol 1998;56:150-7. Council of Europe. European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes. CETS No. 123, 1991 [displayed 30 May 2007] Available at http