Pharmacogenetics and drug metabolism - from rudiments to current for individualised medicine

Main Article Content

Olufunmilayo E. Adejumo
Chinedum P. Babalola

Abstract

Background: A developing branch of study that focuses on the genetic investigation of the pharmacogenes responsible for drug metabolism is known as pharmacogenetics.


Objective: This review, focused on how drug metabolism and new pharmacogenetic testing interact.


Methods: A search of existing literature specifically concerned with the use of knowledge gained from the study of gene variations in selected drug metabolising enzymes to direct the use of drugs and associated therapies was carried out. This was with the view of further research in this rapidly developing subject that will help us move away from the "one size fits all" approach to prescribing and improve our knowledge of the factors that influence individual differences in drug disposition and, ultimately, the efficacy or toxicity of medication responses.


Results: Along with improved therapeutic efficacy and public health, potential advantages would include the achievement of better customized prescribing, better patient outcomes in study populations, and more.


Conclusion: This is done to usher in the new era of medical genetics, also known as genetic medicine, which encompasses fields like personalized medicine, gene therapy, and the rapidly developing medical specialty known as predictive medicine.

Downloads

Download data is not yet available.

Article Details

How to Cite
Adejumo, O. E., & Babalola, C. P. (2023). Pharmacogenetics and drug metabolism - from rudiments to current for individualised medicine. West African Journal of Pharmacy, 33(2), 1 - 20. https://doi.org/10.60787/wapcp-33-2-263
Section
Articles
Author Biography

Chinedum P. Babalola, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Nigeria

Chrisland University, Abeokuta, Ogun state, Nigeria 

How to Cite

Adejumo, O. E., & Babalola, C. P. (2023). Pharmacogenetics and drug metabolism - from rudiments to current for individualised medicine. West African Journal of Pharmacy, 33(2), 1 - 20. https://doi.org/10.60787/wapcp-33-2-263

Share

References

Linder MW, Prough RA, Valdes (Jr) R (1997). Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency. Clinical Chemistry 43: 254-266

Lindpaintner K (2002). Pharmacogenetics and the future of medical practice. British Journal of Clinical Pharmacology 54: 221-230.

Garrod AE (1914). "Medicine from the chemical standpoint". Lancet; ii: 281-289.

Motulsky (1957). Drug reactions, enzymes, and biochemical genetics. Journal of the American Medical Association 165: 835-837.

Kalow W (1962). Pharmacogenetics - Hereditary and the responses to drugs. WB Sauders, Philadelphia P.A.

Meyer UA, Zanger UM (1997). Molecular mechanisms of genetic polymorphisms of drug metabolism. Annual Review of Pharmacology and

Toxicology 37: 269-296.

McLeod HL, Evans WE (2001). Pharmacogenomics: unlocking the human genome for better drug therapy. Annual Review of Pharmacology and Toxicology 41: 101-121.

Weinshilboum R (2003). Inheritance and drug response. New England Journal of Medicine 348: 529-537.

Evans WE, McLeod HL (2003). Pharmacogenomics - Drug Disposition, Drug Targets, and Side Effects. New England Journal of Medicine 348: 538-549

Sadee W (1999). Pharmacogenomics. British Medical Journal 319:1-4.

Deneer V (2009). Paper presented at the 75th conference of the Federation of International Pharmacists FIP), Istanbul, Turkey.

Pirmohamed M (2011). Pharmacogenetics: past, present and future. Drug Discovery Today. 16(19-20): 852-861. doi: 10.1016/j.drudis.2011.08.006.

Wilkinson GR, Guengerich FP, Branch RA (1989). Genetic polymorphism of S-mephenytoin hydroxylation. Pharmacology and Therapeutics 43: 53-76.

Wrighton SA, Stevens JC, Becker GW, VandenBranden M (1993). Isolation and characterization of human liver cytochrome P450 2C19: Correlation between 2 C 19 and S - mepheny to in 49-hydroxylation. Archives of Biochemistry and Biophysics 306: 240-245.

Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM and Ghanayem BI (1994). Evidence for a role for 2C19 in metabolism of S-mephenytoin in humans. Biochemistry 33: 1743-1752.

Brown MP, Buckley MF, Rudzki Z, Oliver IN (2007). Why we will need to learn new skills to control cancer. Internal Medicine Journal 37: 201-204

Kim S, Yun YM, Chae HJ, Cho HJ, Ji M, Kim IS, Wee KA, Lee W, Song SH, Woo HI, Lee SY, Chun S (2017). Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines. Annals of Laboratory Medicine 37(2): 180-193. doi: 10.3343/alm.2017.37.2.180.

Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitlandvan der Zee AH, Mulder H et al. (2011). Pharmacogenetics: from bench to byte--an update of guidelines. Clinical Pharmacology and Therapeutics 89: 662-673.

Valdes R, Payne DA et al. editors. (2010). Laboratory medicine practice guidelines. Laboratory analysis and application of pharmacogenetics to clinical practice. Washington, DC: National Academy of Clinical Biochemistry.

Ruaño G, Valdes R (Jr) (2010). Pharmacology and Population Genetics Considerations and Their Applications in Pharmacogenetics in the National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines (2010) Laboratory Analysis and Application of Pharmacogenetics to Clinical Practice Eds: Valdes R Jr, Payne DA, Linder MW Document (PID 5781) pp 3-10

Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P et al. (2001). The sequence of the human genome. Science 291: 1304-1351.

Weber WW (1997). Pharmacogenetics. Oxford, England: Oxford University Press.

Broder S, Venter JC (2000). Sequencing the entire genomes of free-living organisms. Annual Review of Pharmacology and Toxicology 40: 97-132.

Roses AD (2000). Pharmacogenetics and future drug development and delivery. Lancet 355: 1358-1361.

Risch NJ (2000). Searching for genetic determinants in the new millennium. Nature 405: 847-856.

Chakravarti A (1999). Population genetics: making sense out of sequence. Nature Genetics 21(suppl 1): 5660.

Subramanian G, Adams MD, Venter JC, Broder S (2001) Implications of the human genome for understanding human biology and medicine. Journal of the American Medical Association 286: 2296-2307

Freeman BD, McLeod HL (2004). Challenges of implementing pharmacogenetics in the critical care environment. Nature Review 3: 88-93

Meyer UA (2000). Pharmacogenetics and Adverse Drug Reactions. Lancet 356: 1667-1671

Evans WE, Johnson JA (2001). Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annual Review of Genomics and Human Genetics 2: 9-39.

Evans WE, Relling MV (1999). Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286: 487-491.

Ingelman-Sundberg M, Oscarson M, McLellan RA (1999). Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment. Trends in Pharmacological Sciences 20: 342-349.

Benet LZ, Kroetz DL, Sheiner LB (1996). Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination. In: Hardman JG, Gilman AG, Limbird E, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill Health Professions Division; 3-27.

Wolf GR, Smith G (1999) Pharmacogenetics. British Medical Bulletin 55: 366-386

Nebert DW, Wikvall K, Miller WL (2013). Human cytochromes P450 in health and disease. Philosophical Transactions of the Royal Society

London B: Biological Sciences 368(1612): 20120431. doi: 10.1098/rstb.2012.0431.

Caraco Y (1998). Genetic determinants of drug responsiveness and drug interactions. Therapeutic Drug Monitoring 20: 517-524.

Wilkinson GR (2005). Drug metabolism and variability among patients in drug response. New England Journal of Medicine 352: 2211-2221

Daly AK, Brockmöller J, Broly F, Eichelbaum M, Evans WE, Gonzalez FJ et al. (1996) Nomenclature for human CYP2D6 alleles. Pharmacogenetics 6: 193-201.21.

Werk AN, Lefeldt S, Bruckmueller H, HemmrichStanisak G, Franke A, Roos M et al. (2013). Identification and characterization of a defective CYP3A4 genotype in a kidney transplant patient with severely diminished tacrolimus clearance. Clinical Pharmacology and Therapeutics 95(4): 416-422.doi: 10.1038/clpt.2013.210. Erratum in: Clin Pharmacol Ther. 2014 96(5): 625.

Drögemöller B, Plummer M, Korkie L, Agenbag G, Dunaiski A, Niehaus D et al. (2013). Characterization of the genetic variation present in CYP3A4 in three South African populations. Frontiers in Genetics. 18(4): 17. doi: 10.3389/fgene.2013.00017.

Hu GX, Dai DP, Wang H, Huang XX, Zhou XY, Cai J, Chen H, Cai JP (2017). Systematic screening for CYP3A4 genetic polymorphisms in a Han Chinese population. Pharmacogenomics. 18(4): 369-379. doi: 10.2217/pgs-2016-0179.

Powell NR, Shugg T, Ly RC, Albany C, Radovich M, Schneider BP, Skaar TC (2022). Life-threatening docetaxel toxicity in a patient with reduced-function CYP3A variants: A Case Report. Frontiers in Oncology 31(11): 809527. doi: 10.3389/fonc.2021.80952

Thummel KE, Wilkinson GR (1998). In vitro and in vivo interactions involving human CYP3A. Annual Review of Pharmacology and Toxicology 38:389-430.

Levy RH, Thummel KE, Trager WE, Hansten PD, Eichelbaum M, eds (2000). Metabolic drug interactions. Philadelphia: Lippincott Williams &

Wilkins, 529-543.

Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM (2004). Oral erythromycin and the risk of sudden death from cardiac causes. New England Journal of Medicine 351: 1089-1096.

Martin J (2001). Cytochrome P450 drug interactions: are they clinically relevant? Australian Prescriber 24: 10-12

Daly AK (2003). Pharmacogenetics of the major polymorphic metabolizing enzymes. Fundamental and Clinical Pharmacology 17: 27-41

Bylund J, Ericsson J, Oliw EH (1998) Analysis of cytochrome P450 metabolites of arachidonic and linoleic acids by liquid chromatography-mass spectrometry with ion trap MS. Analytical Biochemistry 265: 55-68.

Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK (1999). Anti-inflammatory Properties of Cytochrome P450 EpoxygenaseDerived Eicosanoids. Science 285: 1276-1279

Klose TS, Blaisdell JA, Goldstein JA. Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J Biochem Mol Toxicol. 1999;13(6):289-95. doi: 10.1002/(sici)1099-0461(1999)13:6<289:

Bahadur N, Leathart JB, Mutch E, Steimel-Crespi D, Dunn SA, Gilissen R, Houdt JV, Hendrickx J, Mannens G, Bohets H, Williams FM, Armstrong M, Crespi CL, Daly AK. CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6alpha-hydroxylase activity in human liver microsomes. Biochem Pharmacol. 2002 Dec 1;64(11):1579-89. doi: 10.1016/s0006-2952(02)01354-0. PMID: 12429347.

Saito Y, Katori N, Soyama A, Nakajima Y, Yoshitani T, Kim SR, Fukushima-Uesaka H, Kurose K, Kaniwa N, Ozawa S, Kamatani N, Komamura K, Kamakura S, Kitakaze M, Tomoike H, Sugai K, Minami N, Kimura H, Goto Y, Minami H, Yoshida T, Kunitoh H, Ohe Y, Yamamoto N, Tamura T, Saijo N, Sawada J. CYP2C8 haplotype structures and their influence on pharmacokinetics of paclitaxel in a Japanese population. Pharmacogenet Genomics. 2007 Jul; 17(7): 461-71. doi: 10.1097/FPC.0b013e32805b72c1.

Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ (1987). cDNA and amino acid sequences of 2 members of the human P450iic gene subfamily. Nucleic Acids Research 15: 10053-10054.

Gaedigk A, Boone EC, Scherer SE, Lee SB, Numanagi? I, Sahinalp C, Smith JD, McGee S, Radhakrishnan A, Qin X, Wang WY, Farrow EG, Gonzaludo N, Halpern AL, Nickerson DA, Miller NA, Pratt VM, Kalman LV. CYP2C8, CYP2C9, and CYP2C19 Characterization Using Next-Generation Sequencing and Haplotype Analysis: A GeT-RM Collaborative Project. J Mol Diagn. 2022, 24 (4): 337-350. doi: 10.1016/j.jmoldx.2021.12.011.

Goldstein JA (2001). Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. British Journal of Clinical Pharmacology 52: 349-355

Dai D, Zeldin DC, Blaisdell JA, Chanas B, Coulter SJ, Ghanayem BI, Goldstein JA (2001). Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics 11: 597-607.

Soyama A, Saito Y, Hanioka N, Murayama N, Nakajima O, Katori N, Ishida S, Sai K, Ozawa S, and Sawada J-I (2001). Non-synonymous single nucleotide alterations found in the CYP2C8 gene result in reduced in vitro paclitaxel metabolism. Biological and Pharmaceutical Bulletin 24: 1427- 1430.

Blaisdell J, Jorge-Nebert LF, Coulter S, Ferguson SS, Lee SJ, Chanas B, Xi T, Mohrenweiser H, Ghanayem B, Goldstein JA. Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics. 2004 Aug; 14 (8): 527 - 37. doi:10.1097/01.fpc.0000114759.08559.51.

Dai DP, Wang YH, Wang SH, Geng PW, Hu LM, Hu GX, Cai JP (2013) In vitro functional characterization of 37 CYP2C9 allelic isoforms found in Chinese Han population. Acta Pharmacologica Sinica (2013) 34: 1449-1456; doi: 10.1038/aps.2013.123

Higashi, MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE (2002). Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. Journal of the American Medical Association 287: 1690-1698

Hillman MA, Wilke RA, Caldwell MD, Berg RL, Glurich I, Burmester JK (2004). Relative impact of covariates in prescribing warfarin according to CYP2C9-based genotype. Pharmacogenetics 14: 539-547.

Gage BF, Eby C, Milligan PE, Banet GA, Duncan JR, McLeod HL (2004). Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Journal of Thrombosis and Haemostasis 91:87-94

Scordo MG, Pengo V, Spina E, Dahl ML, Gusella M, Padrini R (2002). Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clinical Pharmacology and Therapeutics 72: 702-710

Wadelius M, Sörlin K, Wallerman O, Karlsson J, Yue Q-Y, Magnusson PKE, Wadelius C, Melhus H (2004). Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics Journal 4: 40-48

Allabi AC, Gala JL, Horsmans Y, Babaoglu MO, Bozkurt A, Heusterspreute M, Yasar U. Functional impact of CYP2C95, CYP2C96, CYP2C98, and CYP2C911 in vivo among black Africans. Clin Pharmacol Ther. 2004 76(2): 113-8. doi: 10.1016/j.clpt.2004.04.001. 8.

King BP, Khan TI, Aithal GP, Kamali F, Daly AK. Upstream and coding region CYP 2 C 9 polymorphisms: correlation with warfarin dose and

metabolism. Pharmacogenetics. 2004 ;14(12):813-22. doi: 10.1097/00008571-200412000-00004.

Dai DP, Xu RA, Hu LM, Wang SH, Geng PW, Yang JF, Yang LP, Qian JC, Wang ZS, Zhu GH, Zhang XH, Ge RS, Hu GX, Cai JP. CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database. Pharmacogenomics J. 2014 ;14(1):85-92. doi: 10.1038/tpj.2013.2.

Dai DP, Li CB, Wang SH, Cai J, Geng PW, Zhou YF, Hu GX, Cai JP. Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient. Pharmacogenomics. 2015; 16(13):1475-86. doi: 10.2217/pgs.15.89.

Chen H, Dai DP, Zhou S, Liu J, Wang SH, Wu HL, Zhou Q, Geng PW, Chong J, Lü Y, Cai JP, Yang JF. An identification and functional evaluation of a novel CYP2C9 variant CYP2C9*62. Chem Biol Interact. 2020. 25; 327: 109168. doi:10.1016/j.cbi.2020.109168.

Nizamuddin S, Dubey S, Singh S, Sharma S, Machha P, Thangaraj K. CYP2C9 Variations and Their Pharmacogenetic Implications Among Diverse South Asian Populations. Pharmgenomics Pers Med. 2021, 14:135-147. doi: 10.2147/PGPM.S272015.

Chaudhry A S., Prasad B, Shirasaka Y, Fohner A, Finkelstein D, Fan Y, Wang S, Wu G, Aklillu E, Sim S C., Thummel K E., and Schuetz E G. The CYP2C19 Intron 2 Branch Point SNP is the Ancestral Polymorphism Contributing to the Poor Metabolizer Phenotype in Livers with CYP2C19*35 and CYP2C19*2 Alleles. Drug Metab Dispos 43:1226-1235, 2015. http://dx.doi.org/10.1124/dmd.115.064428

Lee CR, Luzum JA, Sangkuhl K, Gammal RS, Sabatine MS, Stein CM, Kisor DF, Limdi NA, Lee YM, Scott SA, Hulot JS, Roden DM, Gaedigk A, Caudle KE, Klein TE, Johnson JA, Shuldiner AR (2022). Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: Update. Clinical Pharmacology & Therapeutics |(Jan 16, epub ahead of print). doi:10.1002/cpt.2526

Gurusamy U, Shewade D G , in Handbook of Pharmacogenomics and Stratified Medicine, 2014. Edited by S andosh Padman abhan. https://doi.org/10.1016/C2010-0-67325-1 pp 323-430

Andersson T, Regardh C-G, Lou Y-C, Zhang Y, Dahl ML and Bertilsson L (1992). Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects. Pharmacogenetics 2: 25-31.

Küpfer A, Branch RA (1985). Stereo selective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. Clinical Pharmacology and Therapeutics 38: 414-418

Adedoyin A, Prakash C, O'Shea D, Blair IA, Wilkinson GR (1994). Stereo selective disposition of hexobarbital and its metabolites: Relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. Pharmacogenetics 4: 27-38.

Baumann P, Jonzier-Perez M, Kerb L, Kupfer A, Tingueley D, Schopf J (1986). Amitriptyline pharmacokinetics and clinical response. II.

Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. International Clinical Psychopharmacology 1: 102-112

Skjelbo E, Brøsen K, Hallas J, Gram LF (1991). The mephenytoin oxidative polymorphism is partially responsible for the N-demethylation of imipramine. Clinical Pharmacology and Therapeutics 49: 18-23.

Sindrup SH, Brøsen K, Hansen MGJ, Aaes-Jorgensen T, Overo KF, Gram LF (1993). Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Therapeutic Drug Monitoring 15: 11-17

Nielsen KK, Brøsen K, Hansen MGJ, Gram LF (1994). Single-dose kinetics of clomipramine: relationship to the sparteine/debrisoquine and S-mephenytoin oxidation polymorphisms. Clinical Pharmacology and Therapeutics 55: 518-527.

Ward SA, Helsby NA, Skjelbo E, Brøsen K, Gram LF, Breckenridge AM (1991). The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation polymorphism--a panel study. British Journal of Clinical Pharmacology 31: 689-692

Ward SA, Watkins WM, Mberu E, Saunders JE, Koech DK, Gilles HM, Howells RE, Breckenridge AM (1989). Inter-subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man. British Journal of Clinical Pharmacology 27:781-787.

Bertilsson L, Henthorn TK, Sanz E, Tybring G, Säwe J, Villén T (1989). Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin but not debrisoquine hydroxylation phenotype. Clinical Pharmacology and Therapeutics 45: 348-355.

Allabi AC, Gala J, Desager J, Heusterspreute M, Horsmans Y (2003). Genetic polymorphisms of CYP2C9 and CYP2C19 in the Beninese and Belgian populations. British Journal of Clinical Pharmacology 56: 653-657

de Morais SM, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA (1994a). Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Molecular Pharmacology 46: 594-598.

de Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA (1994b). The major genetic defect responsible for the polymorphism of Smephenytoin metabolism in humans. Journal of Biological Chemistry 269: 15419-15422.

Wang JH, Liu ZQ, Wang W, Chen XP, Shu Y, He N, Zhou HH (2001). Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clinical Pharmacology and Therapeutics 70: 42-7

Kirchheiner J, Brosen K, Dahl ML, Gram LF, Kasper S, Roots I, Sjoqvist F, Spina E, Brockmoller J (2001). CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatrica Scandinavica 104: 173-92.

Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmoller J (2004). Pharmacogenetics of antidepressant and the antipsychotics: the contribution of allelic variations to the phenotype of drug response. Molecular Psychiatry 9: 442-73

Partovian C, Jacqz-Aigrain E, Keundjian A, Jaillon P, Funck-Brentano C (1995). Comparison of chloroguanide and mephenytoin for the in vivo assessment of genetically determined CYP2C19 activity in humans. Clinical Pharmacology and Therapeutics 58: 257-263

Helsby NA, Ward SA, Edwards G, Howells RE, Breckenridge AM (1990b). The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism. British Journal of Clinical Pharmacology 30: 593-598

Anderson T, Regårdh CG, Dahi-Puustinen ML, Bertilsson L (1990b) Slow omeprazole metabolisers are also poor S-mephenytoin hydroxylators. Ther Drug Monit 12: 416-416

Chiba K, Kobayashi K, Manabe K, Tani M, Kamataki T, Ishizaki T (1993). Oxidative metabolism of omeprazole in human liver microsomes:

Cosegregation with S - m epheny to in 4? - hydroxylation. Journal of Pharmacology and Experimental Therapeutics 266: 52-59.

Bertrand-Thiebault C, Berrahmoune H, Thompson A, Marie B, Droesch S, Siest G, Foernzler D, VisvikisSiest S (2008) Genetic Polymorphism of CYP2C19 Gene in the Stanislas Cohort. A link with Inflammation. Annals of Human Genetics 72: 178-183

Furuta T, K Ohashi, K Kosuge, XJ Zhao, M Takashima, M Kimura, M Nishimoto, H Hanai, E Kaneko, T Ishizaki (1999). CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clinical Pharmacology and Therapeutics 65: 552-61.

Furuta T, Ohashi K, Kamata T, Takashima M, Kosuge K, Kawasaki T, Hanai H, Kubota T, Ishizaki T, Kaneko E (1998). Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer. Annals of Internal Medicine 129: 1027-1030.

Furuta T, Takashima M, Shirai N, Xiao F, Hanai H, Ohashi K, Ishizaki T (2000). Cure of refractory duodenal ulcer and infection caused by Helicobacter pylori by high doses of omeprazole and amoxicillin in a homozygous CYP2C19 extensive metabolizer patient. Clinical Pharmacology and Therapeutics 67: 684

Scott SA, Martis S, Peter I, Kasai Y, Kornreich R, Desnick RJ (2012). Identification of CYP2C19*4B: pharmacogenetic implications for drug

metabolism including clopidogrel responsiveness. Pharmacogenomics Journal 12(4): 297-305. doi: 10.1038/tpj.2011.5.

Caraco Y, Lagerstrom PO, Wood AJ (1996). Ethnic and genetic determinants of omeprazole disposition and effect. Clinical Pharmacology and Therapeutics 60: 157-167.

Watanabe, M, Iwahashi K, Kugoh T, Suwaki H (1998). The relationship between phenytoin pharmacokinetics and the CYP2C19 genotype in Japanese epileptic patients. Clinical Neuropharmacology 21: 122-126.

Kaneko A, Bergqvist Y, Taleo G, Kobayakawa T, Ishizaki T, Bjorkman A (1999). Proguanil disposition and toxicity in malaria patients from Vanuatu with high frequencies of CYP2C19 mutations. Pharmacogenetics 9: 317-326.

PharmGKB. https://www.pharmvar.org/. Accessed September 6, 2022

Twist GP, Gaedigk A, Miller NA, Farrow EG, Willig LK, Dinwiddie DL, Petrikin JE, Soden SE, Herd S, Gibson M, Cakici JA, Riffel AK, Leeder JS,

Dinakarpandian D, Kingsmore SF. Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, CYP2D6, from whole-genome sequences. NPJ Genom Med. 2016 Jan 13; 1: 15007. doi:10.1038/npjgenmed.2015.7. Erratum in: NPJ Genom Med. 2017 1;2:16039.

Marez D, Legrand M, Sabbagh N, Lo Guidice JM, Spire C, Lafitte JJ, Meyer UA, Broly F. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics. 1997 Jun;7(3):193-202. doi: 10.1097/00008571-199706000-00004

Thuerauf N, Lunkenheimer J (2006). The impact of the CYP2D6 - polymorphism on dose recommendations for current antidepressants. European Archives of Psychiatry and Clinical Neuroscience 256: 287-293.

Shams ME, Arneth B, Hiemke C, Dragicevic A, Muller MJ, Kaiser R, Lackner K, Hartter S (2006) CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. Journal of Clinical Pharmacy and Therapeutics 31: 493-502.

Cho Y, Lee B (2006). Pharmacokinetics and bioequivalence evaluation of risperidone in healthy male subjects with different CYP2D6

genotypes. Archives of Pharmacal Research 29:525-533.

Kearns GL (2002). Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation. Journal of Clinical Pharmacology 42: 24-29

Wang G, Zhang H, He F, Fang X, Wang S, Lai M, Huang J (2006). Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol

analgesia in a Chinese population. European Journal of Clinical Pharmacology 62: 927-931.

Kirchheiner J, Schmidt H, Tzvetkov M, Keulen JT, Lotsch J, Roots I, Brockmoller J (2006). Pharmacokinetics of codeine and its metabolite

morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics Journal 7: 257-265

Goetz, MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW et al. (2005). Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. Journal of Clinical Oncology 23: 9312-9318.

Kimura S, Umeno M, Skoda RC, Meyer UA, Gonzalez FJ (1989). The human Debrisoquine 4- hydroxylase (CYP2D) locus: sequence and

identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. American Journal of Human Genetics 45: 889-904.

Schwartz JB (2002). Pharmacogenetics: Has it reached the clinics? Journal of Gender Specific Medicine 5: 13-18

Cascorbi I (2003). Pharmacogenetics of cytochrome p4502D6: Genetic background and clinical implication. European Journal of Clinical

Investigation 33: 17-22.

Ingelman-Sundberg M (2005). Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary

aspects and functional diversity. Pharmacogenomics Journal 5: 6-13.

Xie H-G, Kim RB, Wood AJJ, Stein CM. (2001). Molecular basis of ethnic differences in drug disposition and response. Annual Review of

Pharmacology and Toxicology 41:815-50.

Bertilsson L (1995). Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clinical Pharmacokinetics 29: 192-209.

Griese EU, Ilett KF, Kitteringham NR, Eichelbaum M, Powell H, Spargo RM, LeSouef PN, Musk AW, Minchin RF (2001). Allele and genotype

frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in Aborigines from Western Australia. Pharmacogenetics 11: 69-76

Masimirembwa C, Persson I, Bertilsson L, Hasler J, Ingelman-Sundberg M (1996). A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. British Journal of Clinical Pharmacology 42: 713-719.4

Meyer UA, Zanger UM, Grant D, Blum M (1990). Genetic polymorphisms of drug metabolism. Advances in Drug Research 19: 197-217

Relling MV, Cherrie J, Schell MJ, Petros WP, Meyer WH, Evans WE (1991). Lower prevalence of the debrisoquin oxidative poor metabolizer

phenotype in American black versus white subjects. Clinical Pharmacology and Therapeutics 50: 308-313.

Woolhouse NM (1986b). The debrisoquine} sparteine oxidation polymorphism: Evidence of genetic heterogeneity among Ghanaians. In: Kalow W, Goedde HW, Agarwal DP (Eds.), Ethnic Differences in Reactions to Drugs and Xenobiotics (pp. 189-206). New York: Alan R. Liss, Inc

Mbanefo C, Bababunmi EA, Mahgoub A, Sloan TP, Idle JR, Smith RL (1980). A study of the debrisoquine hydroxylation polymorphism in a

Nigerian population. Xenobiotica 10(11): 811-818.

Iyun AO, Lennard MS, Tucker GT, Woods HF (1986). Metoprolol and debrisoquin metabolism in Nigerians: lack of evidence for polymorphic oxidation. Clinical Pharmacology & Therapeutics 40(4): 387-394.

Lennard MS, Iyun AO, Jackson PR, Tucker GT, Woods HF (1992). Evidence for a dissociation in the control of sparteine, debrisoquine and

metroprolol metabolism in Nigerians. Pharmacogenetics 2: 89-92

Nsabiyumva F, Faret Y, Autret E, Jonville AP, Breteau M (1991). Oxidative polymorphism of dextromethorphan in a Burundi population.

European Journal of Clinical Pharmacology 41: 75-77

Sommers De K, Moncrieff J, Avenant J (1990). Polymorphism in sparteine oxidation in the Barakwena (Kwengo) of Southern Africa. South African Journal of Science 86: 28-29.

Sommers De K, Moncrieff J, Avenant JC (1991). Absence of polymorphism of sparteine oxidation in the South African Venda. Human Experimental Toxicology 10: 175-178.

Masimirembwa C, Hasler J, Bertilsson L, JohanssonI, Ekberg O, Ingelman-Sundberg M (1996a). Phenotype and genotype analysis of debrisoquine hydroxylase (CYP2D6) in black Zimbabwean population: reduced enzyme activity and evaluation of metabolic correlation of CP2D6 probe drugs. European Journal of Clinical Pharmacology 51: 117-122.

Bradford LD, Kirlin WG (1998) Polymorphism of CYP2D6 in Black populations: implications for psychopharmacology. International Journal of Neuropsychopharmacology 1: 173-185

Aklillu E, Persson I, Bertilsson L, Johansson I, Rodrigues F, Ingelman-Sundberg M (1996). Frequent Distribution of Ultrarapid Metabolizers of Debrisoquine in an Ethiopian Population Carrying Duplicated and Multiduplicated Functional CYP2D6 Alleles. The Journal of

Pharmacology and Experimental Therapeutics 278(1): 441-446

Ahmed JH, Makonnen E, Fotoohi A, Aseffa A, Howe R, Aklillu E (2019). CYP2D6 Genotype Predicts Plasma Concentrations of Tamoxifen Metabolites in Ethiopian Breast Cancer Patients. Cancers 11:1353; doi:10.3390/cancers11091353

Rajman I, Knapp L, Morgan T, Masimirembwa C (2017). African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development. eBioMedicine 17: 67-74. https://doi.org/10.1016/j.ebiom.2017.02.017

Robbins DK, Wedlund PJ, Kuhn R, Baumann RJ, Levy RH, Chang SL (1990). Inhibition of epoxide hydrolase by valproic acid in epileptic patients receiving carbamazepine. British Journal of Clinical Pharmacology 29: 759-762

Desta Z, Zhao X, Shin JG, Flockhart DA (2002). Clinical significance of the cytochrome P450 2C19genetic polymorphism. Clinical

Pharmacokinetics 41: 913-958.

Edstein MD, Shanks GD, Teja-Isavadharm P, Rieckmann KH, Webster HK (1994). Oxidative activation of proguanil and dapsone acetylation in Thai soldiers. British Journal of Clinical Pharmacology 37: 67-70.

Brøsen K, Skjelbo E, Flachs H (1993b). Proguanil metabolism is determined by the mephenytoin oxidation polymorphism in Vietnamese living in Denmark. British Journal of Clinical Pharmacology 36: 105-108.

Basci NE, Bozkurt A, Kortunay S, Isimar A, Sayal A, Kayaalp SO (1996). Proguanil metabolism in relation to S-mephenytoin oxidation in a Turkish population. British Journal of Clinical Pharmacology 42: 771-773

Skjelbo E, Mutabingwa TK, Bygbjerg I, Nielsen KK, Gram LF, Brøsen K (1996). Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians. Clinical Pharmacology and Therapeutics 59: 304-311.

Bathum L, Skjelbo E, Mutabingwa TK, Madsen H, Horder M, Brosen K (1999). Phenotypes and genotypes for CYP2D6 and CYP2C19 in a black Tanzanian population. British Journal of Clinical Pharmacology 48: 395-401

Watkins WM, Mberu EK, Nevill CG, Ward SA, Breckenridge AM, Koech DK (1990). Variability in the metabolism of proguanil to the active

metabolite cycloguanil in healthy Kenyan adults. Transactions of the Royal Society of Tropical Medicine and Hygiene 84: 492-495

Bolaji OO, Sadare IO, Babalola CP, Ogunbona FA (2002). Polymorphic oxidative metabolism of proguanil in a Nigerian population. European Journal of Clinical Pharmacology 58: 543-545.

Adejumo OE, Kotila TR, Falusi AG, Silva BO, Nwogu JN, Fasinu PS, Babalola CP (2016). Phenotyping and genotyping of CYP2C19 using comparative metabolism of proguanil in sickle-cell disease patients and healthy controls in Nigeria. Pharmacology Research and Perspectives 4(5): s e00252, doi: 10.1002/prp2.252.

Babalola CP, Adejumo O, Ung D, Xu Z, Odetunde A, Kotila T, Falusi AG, Nagar S (2010). Cytochrome P450 CYP2C19 genotypes in Nigerian sickle-cell disease patients and normal controls. Journal of Clinical Pharmacy and Therapeutics 35: 471-477 doi:10.1111/j.1365-2710.2009.01122.x.

Nikolin B, Imamovi? B, Medanhodzi?-Vuk S, Sober M ( 2 0 0 4 ) . H i g h p e r f o r m a n c e l i q u i d chromatography in pharmaceutical analyses. Bosnian Journal of Basic Medical Sciences 4: 5-9.

Kobayashi K, Chiba K, Yagi T, Shimada N, Taniguchi T, Horie T, Tani M, Yamamoto T, Ishizaki T, Kuroiwa Y (1997). Idenfitication of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. Journal of Pharmacology and Experimental Therapeutics 280: 927-933.

Tamminga WJ, Wemer J, Oosterhuis B, Weiling J, Wilffert B, de Leij LF, de Zeeuw RA, Jonkman JH (1999). CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. European Journal of Clinical

Pharmacology 55(3): 177-184. doi:10.1007/s002280050615.

Lagerstrom P0, Persson BA (1984). Determination of omeprazole and metabolites in plasma and urine by liquid chromatography. Journal of Chromatography 309: 347-356.

Yim D-S, Jeong JE, Park JY (2001) Assay of omeprazole and omeprazole sulfone by semimicrocolumn liquid chromatography with mixedfunction precolumn. J Chromatography B: Biomedical Sciences and Applications 754: 487-493

Tybring G, Böttiger Y, Widén J, Bertilsson L (1997). Enantioselective hydroxylation of omeprazole catalyzed by CYP2C19 in Swedish white subjects. Clinical Pharmacology and Therapeutics 62: 129-137.

Shimizu M, Uno T, Niioka T, Yaui-Furukori N, Takahata T, Sugawara K, Tateishi T (2006). Sensitive determination of omeprazole and its two main metabolites in human plasma by column-switching high-performance liquid chromatography: Application to pharmacokinetic study in relation to CYP2C19 genotypes. Journal of Chromatography B 832: 241-248

Kanazawa H, Okada A, Matsushima Y, Yokota H, Okubo S, Mashige F, Nakahara K (2002). Determination of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry. Journal of Chromatography A 949: 1-9

Macek J, Klíma J, Ptá?ek P (2007). Rapid determination of omeprazole in human plasma by protein precipitation and liquid chromatography tandem mass spectrometry. Journal of Chromatography B 852(1-2): 282-287. https://doi.org/10.1016/j.jchromb.2007.01.026

Gafni I, Nolte H, Tyndale R et al. (2001) Resolving the roles of CYP2C19 and CYP3A4 in the metabolism of omeprazole in vivo using chronic omeprazole and ketoconazole. Federation of American Societies for Experimental Biology Journal 15: A918

Kimura M, Ieiri I, Wada Y, Maiya K, Urae A, Iimori E, Sakai T, Otsubo K, Higuchi S (1999). Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy. British Journal of Clinical Pharmacology 47: 115-119

Chen B, Gagnon M, Shanhangian S, Anderson NL, Howerton DA, Boone DJ (2009). Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions. Morbidity and Mortality Weekly Report 58: 1-36.

Payne DA, Carr J (2010). Methodology and Quality Assurance Considerations in Pharmacogenetic Testing in The National Academy of Clinical Biochemistry: Laboratory Medicine Practice Guidelines Laboratory Analysis and Application of Pharmacogenetics to Clinical Practice Edited by Roland Valdes, Jr., Deborah Payne, and Mark W.Linder Chapter 3, pp 11-13

International Organisation for Standardisations' Technical Committee (ISO 15189) (2003). http://global.ihs.com assessed 6 Sept 2022

Chen B, O'Connell CD, Boone DJ, Amos JA, Beck JC, Chan MM, Farkas DH, Lebo RV, Richards CS, Roa BB et al. (2005). The Quality Control Materials for Genetic Testing Group developing a sustainable process to provide quality control materials for genetic testing. Genetic Medicine 7: 534-549. DOI: 10.1097/01.gim.0000183043.94406.81

Auwerx C, Sadler MC, Reymond A, Kutalik Z (2022). From pharmacogenetics to pharmaco-omics: Milestones and future directions. Human Genetics and Genomics Advances 3: 100100. https://doi.org/10.1016/j.xhgg.2022.100100

Similar Articles

You may also start an advanced similarity search for this article.