1932

Abstract

Pharmacogenetics is a key component of precision medicine. Genetic variation in drug metabolism enzymes can lead to variable exposure to drugs and metabolites, potentially leading to inefficacy and drug toxicity. Although the evidence for pharmacogenetic associations in children is not as extensive as for adults, there are several drugs across diverse therapeutic areas with robust pediatric data indicating important, and relatively common, drug–gene interactions. Guidelines to assist gene-based dose optimization are available for codeine, thiopurine drugs, selective serotonin reuptake inhibitors, atomoxetine, tacrolimus, and voriconazole. For each of these drugs, there is an opportunity to clinically implement precision medicine approaches with children for whom genetic test results are known or are obtained at the time of prescribing. For many more drugs that are commonly used in pediatric patients, additional investigation is needed to determine the genetic factors influencing appropriate dose.

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2020-01-06
2024-04-14
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Literature Cited

  1. 1. 
    Abrahams E. 2008. Right drug—right patient—right time: personalized medicine coalition. Clin. Transl. Sci. 1:111–12
    [Google Scholar]
  2. 2. 
    Stark Z, Dolman L, Manolio TA, Ozenberger B, Hill SL et al. 2018. Integrating genomics into healthcare: a global responsibility. Am. J. Hum. Genet. 104:113–20
    [Google Scholar]
  3. 3. 
    Hines RN. 2013. Developmental expression of drug metabolizing enzymes: impact on disposition in neonates and young children. Int. J. Pharm. 452:1–23–7
    [Google Scholar]
  4. 4. 
    Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K et al. 2012. Pharmacogenomics knowledge for personalized medicine. Clin. Pharmacol. Ther. 92:4414–17
    [Google Scholar]
  5. 5. 
    Relling MV, Klein TE. 2011. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin. Pharmacol. Ther. 89:3464–67
    [Google Scholar]
  6. 6. 
    Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH et al. 2011. Pharmacogenetics: from bench to byte—an update of guidelines. Clin. Pharmacol. Ther. 89:5662–73
    [Google Scholar]
  7. 7. 
    Yang JJ, Landier W, Yang W, Liu C, Hageman L et al. 2015. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J. Clin. Oncol. 33:111235–42
    [Google Scholar]
  8. 8. 
    Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM et al. 2015. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin. Pharmacol. Ther. 98:119–24
    [Google Scholar]
  9. 9. 
    Van Driest SL, Shi Y, Bowton E, Schildcrout J, Peterson J et al. 2014. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin. Pharmacol. Ther. 95:4423–31
    [Google Scholar]
  10. 10. 
    Caudle KE, Dunnenberger HM, Freimuth RR, Peterson JF, Burlison JD et al. 2017. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet. Med. 19:2215–23
    [Google Scholar]
  11. 11. 
    DailyMed 2019. Codeine sulfate—codeine sulfate tablet Fact Sheet, DailyMed, Natl. Lib. Med Bethesda, MD: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=010905f9-3bcb-4b50-9fe8-a3ad0010f14c
  12. 12. 
    DailyMed 2019. Oxycodone hydrochloride—oxycodone hydrochloride solution Fact Sheet, DailyMed, Natl. Lib. Med Bethesda, MD: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c193a56a-bb8f-476d-b1ec-789fd2aaef7e
  13. 13. 
    DailyMed 2019. Acetaminophen and codeine phosphate—acetaminophen and codeine phosphate liquid Fact Sheet, DailyMed, Natl. Lib. Med Bethesda, MD: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bca1d24-a317-44c4-8db2-68030eb961ed
  14. 14. 
    Sevelius H, Colmore JP. 1966. Objective assessment of antitussive agents in patients with chronic cough. J. New Drugs 6:4216–23
    [Google Scholar]
  15. 15. 
    Sevelius H, McCoy JF, Colmore JP 1971. Dose response to codeine in patients with chronic cough. Clin. Pharmacol. Ther. 12:3449–55
    [Google Scholar]
  16. 16. 
    Freestone C, Eccles R. 1997. Assessment of the antitussive efficacy of codeine in cough associated with common cold. J. Pharm. Pharmacol. 49:101045–49
    [Google Scholar]
  17. 17. 
    Hutchings HA, Eccles R. 1994. The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects. Eur. Respir. J. 7:4715–19
    [Google Scholar]
  18. 18. 
    Smith J, Owen E, Earis J, Woodcock A 2006. Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 117:4831–35
    [Google Scholar]
  19. 19. 
    Mignat C, Wille U, Ziegler A 1995. Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci 56:10793–99
    [Google Scholar]
  20. 20. 
    Volpe DA, McMahon Tobin GA, Mellon RD, Katki AG, Parker RJ et al. 2011. Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs. Regul. Toxicol. Pharmacol. 59:3385–90
    [Google Scholar]
  21. 21. 
    Gaedigk A, Sangkuhl K, Whirl-Carrillo M, Klein T, Leeder JS 2017. Prediction of CYP2D6 phenotype from genotype across world populations. Genet. Med. 19:169–76
    [Google Scholar]
  22. 22. 
    Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE et al. 2014. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin. Pharmacol. Ther. 95:4376–82
    [Google Scholar]
  23. 23. 
    Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD et al. 2012. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin. Pharmacol. Ther. 91:2321–26
    [Google Scholar]
  24. 24. 
    Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ 2006. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 368:9536704
    [Google Scholar]
  25. 25. 
    Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G 2009. Codeine, ultrarapid-metabolism genotype, and postoperative death. N. Engl. J. Med. 361:8827–28
    [Google Scholar]
  26. 26. 
    Ferreirós N, Dresen S, Hermanns-Clausen M, Auwaerter V, Thierauf A et al. 2009. Fatal and severe codeine intoxication in 3-year-old twins—interpretation of drug and metabolite concentrations. Int. J. Legal Med. 123:5387–94
    [Google Scholar]
  27. 27. 
    Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C et al. 2012. More codeine fatalities after tonsillectomy in North American children. Pediatrics 129:5e1343–47
    [Google Scholar]
  28. 28. 
    Friedrichsdorf SJ, Nugent AP, Strobl AQ 2013. Codeine-associated pediatric deaths despite using recommended dosing guidelines: three case reports. J. Opioid Manag. 9:2151–55
    [Google Scholar]
  29. 29. 
    Voronov P, Przybylo HJ, Jagannathan N 2007. Apnea in a child after oral codeine: a genetic variant—an ultra-rapid metabolizer. Pediatr. Anaesth. 17:7684–87
    [Google Scholar]
  30. 30. 
    Madadi P, Ross CJD, Hayden MR, Carleton BC, Gaedigk A et al. 2009. Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin. Pharmacol. Ther. 85:131–35
    [Google Scholar]
  31. 31. 
    Prows CA, Zhang X, Huth MM, Zhang K, Saldaña SN et al. 2014. Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study. Laryngoscope 124:51242–50
    [Google Scholar]
  32. 32. 
    Khetani JD, Madadi P, Sommer DD, Reddy D, Sistonen J et al. 2012. Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study. Pediatr. Drugs 14:6411–15
    [Google Scholar]
  33. 33. 
    Yue QY, Svensson JO, Alm C, Sjöqvist F, Säwe J 1989. Codeine O-demethylation co-segregates with polymorphic debrisoquine hydroxylation. Br. J. Clin. Pharmacol. 28:6639–45
    [Google Scholar]
  34. 34. 
    Williams DG, Patel A, Howard RF 2002. Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br. J. Anaesth. 89:6839–45
    [Google Scholar]
  35. 35. 
    Sistonen J, Madadi P, Ross CJ, Yazdanpanah M, Lee JW et al. 2012. Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers. Clin. Pharmacol. Ther. 91:4692–99
    [Google Scholar]
  36. 36. 
    Food Drug Admin 2013. Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. Drug Saf. Commun., US Food Drug Admin Silver Spring, MD: https://www.fda.gov/media/85072/download
  37. 37. 
    Cavallari LH, Van Driest SL, Prows CA, Bishop JR, Limdi NA et al. 2019. Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing. Genet. Med 21:225563
    [Google Scholar]
  38. 38. 
    Gammal RS, Crews KR, Haidar CE, Hoffman JM, Baker DK et al. 2016. Pharmacogenetics for safe codeine use in sickle cell disease. Pediatrics 138:1e20153479
    [Google Scholar]
  39. 39. 
    Gammal RS, Caudle KE, Quinn CT, Wang WC, Gaedigk A et al. 2019. The case for pharmacogenetics-guided prescribing of codeine in children. Clin. Pharmacol. Ther. 105:61300–2
    [Google Scholar]
  40. 40. 
    Jerome J, Solodiuk JC, Sethna N, McHale J, Berde C 2014. A single institution's effort to translate codeine knowledge into specific clinical practice. J. Pain Symptom Manag. 48:1119–26
    [Google Scholar]
  41. 41. 
    Livingstone MJ, Groenewald CB, Rabbitts JA, Palermo TM 2017. Codeine use among children in the United States: a nationally representative study from 1996 to 2013. Pediatr. Anaesth. 27:119–27
    [Google Scholar]
  42. 42. 
    Van Cleve WC. 2017. Pediatric posttonsillectomy analgesia before and after the black box warning against codeine use. JAMA Otolaryngol 143:101052–54
    [Google Scholar]
  43. 43. 
    de Beaumais TA, Jacqz-Aigrain E 2012. Intracellular disposition of methotrexate in acute lymphoblastic leukemia in children. Curr. Drug Metab. 13:6822–34
    [Google Scholar]
  44. 44. 
    Zaza G, Cheok M, Krynetskaia N, Thorn C, Stocco G et al. 2010. Thiopurine pathway. Pharmacogenet. Genom. 20:9573–74
    [Google Scholar]
  45. 45. 
    Weinshilboum R. 2001. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab. Dispos. 29:4601–5
    [Google Scholar]
  46. 46. 
    Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC et al. 1999. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J. Natl. Cancer Inst. 91:232001–8
    [Google Scholar]
  47. 47. 
    Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui C-H et al. 2018. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin. Pharmacol. Ther. 105:51095–105
    [Google Scholar]
  48. 48. 
    Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui C-H et al. 2013. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin. Pharmacol. Ther. 93:4324–25
    [Google Scholar]
  49. 49. 
    Weinshilboum RM, Sladek SL. 1980. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am. J. Hum. Genet. 32:5651–62
    [Google Scholar]
  50. 50. 
    Walker GJ, Harrison JW, Heap GA, Voskuil MD, Andersen V et al. 2019. Association of genetic variants in NUDT15 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease. JAMA 321:8773–85
    [Google Scholar]
  51. 51. 
    Tanaka Y, Kato M, Hasegawa D, Urayama KY, Nakadate H et al. 2015. Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia. Br. J. Haematol. 171:1109–15
    [Google Scholar]
  52. 52. 
    Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA et al. 2016. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat. Genet. 48:4367–73
    [Google Scholar]
  53. 53. 
    Matimba A, Li F, Livshits A, Cartwright CS, Scully S et al. 2014. Thiopurine pharmacogenomics: association of SNPs with clinical response and functional validation of candidate genes. Pharmacogenomics 15:4433–47
    [Google Scholar]
  54. 54. 
    Stocco G, Franca R, Verzegnassi F, Londero M, Rabusin M, Decorti G 2012. Multilocus genotypes of relevance for drug metabolizing enzymes and therapy with thiopurines in patients with acute lymphoblastic leukemia. Front. Genet. 3:309
    [Google Scholar]
  55. 55. 
    Hareedy MS, El Desoky ES, Woillard J-B, Thabet RH, Ali AM et al. 2015. Genetic variants in 6-mercaptopurine pathway as potential factors of hematological toxicity in acute lymphoblastic leukemia patients. Pharmacogenomics 16:101119–34
    [Google Scholar]
  56. 56. 
    March J, Silva S, Petrycki S, Curry J, Wells K et al. 2004. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. JAMA 292:7807–20
    [Google Scholar]
  57. 57. 
    Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR et al. 2008. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA 299:8901–13
    [Google Scholar]
  58. 58. 
    Findling RL, McNamara NK, Stansbrey RJ, Feeny NC, Young CM et al. 2006. The relevance of pharmacokinetic studies in designing efficacy trials in juvenile major depression. J. Child Adolesc. Psychopharmacol. 16:1–2131–45
    [Google Scholar]
  59. 59. 
    DailyMed 2019. Fluoxetine—fluoxetine capsules capsule Fact Sheet, DailyMed, Natl. Lib. Med Bethesda, MD: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=59de2889-c3d3-4ebf-8826-13f30a3fa439
  60. 60. 
    DailyMed 2019. Fluvoxamine maleate—fluvoxamine maleate tablet, film coated Fact Sheet, DailyMed, Natl. Lib. Med Bethesda, MD: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=85b61f83-ab47-470d-8673-02fea29247be
  61. 61. 
    Chang M, Tybring G, Dahl M-L, Lindh JD 2014. Impact of cytochrome P450 2C19 polymorphisms on citalopram/escitalopram exposure: a systematic review and meta-analysis. Clin. Pharmacokinet. 53:9801–11
    [Google Scholar]
  62. 62. 
    Jukić MM, Haslemo T, Molden E, Ingelman-Sundberg M 2018. Impact of CYP2C19 genotype on escitalopram exposure and therapeutic failure: a retrospective study based on 2,087 patients. Am. J. Psychiatry 175:5463–70
    [Google Scholar]
  63. 63. 
    Aldrich SL, Poweleit EA, Prows CA, Martin LJ, Strawn JR, Ramsey LB 2019. Influence of CYP2C19 metabolizer status on escitalopram/citalopram tolerability and response in youth with anxiety and depressive disorders. Front. Pharmacol. 10:99
    [Google Scholar]
  64. 64. 
    Hicks JK, Bishop JR, Sangkuhl K, Müller DJ, Ji Y et al. 2015. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin. Pharmacol. Ther. 98:2127–34
    [Google Scholar]
  65. 65. 
    Wang JH, Liu ZQ, Wang W, Chen XP, Shu Y et al. 2001. Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin. Pharmacol. Ther 70:142–47
    [Google Scholar]
  66. 66. 
    Rudberg I, Hermann M, Refsum H, Molden E 2008. Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur. J. Clin. Pharmacol. 64:121181–88
    [Google Scholar]
  67. 67. 
    Brandl EJ, Tiwari AK, Zhou X, Deluce J, Kennedy JL et al. 2014. Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. Pharmacogenomics J 14:2176–81
    [Google Scholar]
  68. 68. 
    Yuce-Artun N, Baskak B, Ozel-Kizil ET, Ozdemir H, Uckun Z et al. 2016. Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients. Int. J. Clin. Pharm. 38:2388–94
    [Google Scholar]
  69. 69. 
    Vitiello B, Ordóñez AE. 2016. Pharmacological treatment of children and adolescents with depression. Expert Opin. Pharmacother. 17:172273–79
    [Google Scholar]
  70. 70. 
    Gassó P, Rodríguez N, Mas S, Pagerols M, Blázquez A et al. 2014. Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients. Pharmacogenomics J 14:5457–62
    [Google Scholar]
  71. 71. 
    Ramsey LB, Prows CA, Zhang K, Saldaña SN, Sorter MT et al. 2019. Implementation of pharmacogenetics at Cincinnati Children's Hospital Medical Center: lessons learned over 14 years of personalizing medicine. Clin. Pharmacol. Ther. 105:149–52
    [Google Scholar]
  72. 72. 
    Bousman CA, Dunlop BW. 2018. Genotype, phenotype, and medication recommendation agreement among commercial pharmacogenetic-based decision support tools. Pharmacogenomics J 18:5613–22
    [Google Scholar]
  73. 73. 
    Bousman CA, Jaksa P, Pantelis C 2017. Systematic evaluation of commercial pharmacogenetic testing in psychiatry: a focus on CYP2D6 and CYP2C19 allele coverage and results reporting. Pharmacogenetics Genom 27:11387–93
    [Google Scholar]
  74. 74. 
    Zeier Z, Carpenter LL, Kalin NH, Rodriguez CI, McDonald WM et al. 2018. Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. Am. J. Psychiatry 175:9873–86
    [Google Scholar]
  75. 75. 
    Zerbe RL, Rowe H, Enas GG, Wong D, Farid N, Lemberger L 1985. Clinical pharmacology of tomoxetine, a potential antidepressant. J. Pharmacol. Exp. Ther. 232:1139–43
    [Google Scholar]
  76. 76. 
    Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG et al. 2002. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 27:5699–711
    [Google Scholar]
  77. 77. 
    Dinh JC, Pearce RE, Van Haandel L, Gaedigk A, Leeder JS 2016. Characterization of atomoxetine biotransformation and implications for development of PBPK models for dose individualization in children. Drug Metab. Dispos. Biol. Fate Chem. 44:71070–79
    [Google Scholar]
  78. 78. 
    Brown JT, Abdel-Rahman SM, van Haandel L, Gaedigk A, Lin YS, Leeder JS 2016. Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD. Clin. Pharmacol. Ther. 99:6642–50
    [Google Scholar]
  79. 79. 
    Michelson D, Read HA, Ruff DD, Witcher J, Zhang S, McCracken J 2007. CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. J. Am. Acad. Child Adolesc. Psychiatry 46:2242–51
    [Google Scholar]
  80. 80. 
    Trzepacz PT, Williams DW, Feldman PD, Wrishko RE, Witcher JW, Buitelaar JK 2008. CYP2D6 metabolizer status and atomoxetine dosing in children and adolescents with ADHD. Eur. Neuropsychopharmacol. 18:279–86
    [Google Scholar]
  81. 81. 
    Brown JT, Bishop JR, Sangkuhl K, Nurmi EL, Mueller DJ et al. 2019. Clinical Pharmacogenetics Implementation Consortium Guideline for cytochrome P450 (CYP)2D6 genotype and atomoxetine therapy. . Clin. Pharmacol. Ther. 106:94102
    [Google Scholar]
  82. 82. 
    Ramoz N, Boni C, Downing AM, Close SL, Peters SL et al. 2009. A haplotype of the norepinephrine transporter (Net) gene Slc6a2 is associated with clinical response to atomoxetine in attention-deficit hyperactivity disorder (ADHD). Neuropsychopharmacology 34:92135–42
    [Google Scholar]
  83. 83. 
    Brown JT, Bishop JR. 2015. Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability. Pharmacogenomics 16:131513–20
    [Google Scholar]
  84. 84. 
    Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB 2013. PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet. Genom. 23:10563–85
    [Google Scholar]
  85. 85. 
    Birdwell KA, Grady B, Choi L, Xu H, Bian A et al. 2012. The use of a DNA biobank linked to electronic medical records to characterize pharmacogenomic predictors of tacrolimus dose requirement in kidney transplant recipients. Pharmacogenet. Genom. 22:132–42
    [Google Scholar]
  86. 86. 
    Haufroid V, Mourad M, Van Kerckhove V, Wawrzyniak J, De Meyer M et al. 2004. The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 14:3147–54
    [Google Scholar]
  87. 87. 
    Thervet E, Loriot MA, Barbier S, Buchler M, Ficheux M et al. 2010. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin. Pharmacol. Ther. 87:6721–26
    [Google Scholar]
  88. 88. 
    Pallet N, Etienne I, Buchler M, Bailly E, Hurault de Ligny B et al. 2016. Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype. Am. J. Transplant. 16:92670–75
    [Google Scholar]
  89. 89. 
    Min S, Papaz T, Lafreniere-Roula M, Nalli N, Grasemann H et al. 2018. A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation. Pediatr. Transplant. 22:71–9
    [Google Scholar]
  90. 90. 
    Elens L, Bouamar R, Hesselink DA, Haufroid V, Van Der Heiden IP et al. 2011. A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus pharmacokinetics in kidney transplant recipients. Clin. Chem. 57:111574–83
    [Google Scholar]
  91. 91. 
    Caraballo PJ, Hodge LS, Bielinski SJ, Stewart AK, Farrugia G et al. 2017. Multidisciplinary model to implement pharmacogenomics at the point of care. Genet. Med. 19:4421–29
    [Google Scholar]
  92. 92. 
    Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S et al. 2016. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 63:4e1–60
    [Google Scholar]
  93. 93. 
    Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA et al. 2016. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 62:4e1–50
    [Google Scholar]
  94. 94. 
    Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R et al. 2002. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin. Infect. Dis. 34:5563–71
    [Google Scholar]
  95. 95. 
    Hamada Y, Seto Y, Yago K, Kuroyama M 2012. Investigation and threshold of optimum blood concentration of voriconazole: a descriptive statistical meta-analysis. J. Infect. Chemother. 18:4501–7
    [Google Scholar]
  96. 96. 
    Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O 2008. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin. Infect. Dis. 46:2201–11
    [Google Scholar]
  97. 97. 
    Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N 2006. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J. Clin. Pharmacol. 46:2235–43
    [Google Scholar]
  98. 98. 
    Kadam RS, Van Den Anker JN 2016. Pediatric clinical pharmacology of voriconazole: role of pharmacokinetic/pharmacodynamic modeling in pharmacotherapy. Clin. Pharmacokinet. 55:91031–43
    [Google Scholar]
  99. 99. 
    Moriyama B, Obeng AO, Barbarino J, Penzak SR, Henning SA et al. 2017. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2C19 and voriconazole therapy. Clin. Pharmacol. Ther. 102:145–51
    [Google Scholar]
  100. 100. 
    Cendejas-Bueno E, Borobia AM, Gomez-Lopez A, Escosa-García L, Río-García M et al. 2016. Invasive aspergillosis in a paediatric allogeneic stem cell transplantation recipient owing to a susceptible Aspergillus fumigatus: treatment failure with high doses of voriconazole and influence of CYP2C19 polymorphisms. Int. J. Antimicrob. Agents 47:5410–11
    [Google Scholar]
  101. 101. 
    Hicks JK, Crews KR, Flynn P, Haidar CE, Daniels CC et al. 2014. Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes. Pharmacogenomics 15:81065–78
    [Google Scholar]
  102. 102. 
    Hicks JK, Gonzalez BE, Zembillas AS, Kusick K, Murthy S et al. 2016. Invasive Aspergillus infection requiring lobectomy in a CYP2C19 rapid metabolizer with subtherapeutic voriconazole concentrations. Pharmacogenomics 17:7663–67
    [Google Scholar]
  103. 103. 
    Mori M, Kobayashi R, Kato K, Maeda N, Fukushima K et al. 2015. Pharmacokinetics and safety of voriconazole intravenous-to-oral switch regimens in immunocompromised Japanese pediatric patients. Antimicrob. Agents Chemother. 59:21004–13
    [Google Scholar]
  104. 104. 
    Narita A, Muramatsu H, Sakaguchi H, Doisaki S, Tanaka M et al. 2013. Correlation of CYP2C19 phenotype with voriconazole plasma concentration in children. J. Pediatr. Hematol. Oncol. 35:5e219–23
    [Google Scholar]
  105. 105. 
    Teusink A, Vinks A, Zhang K, Davies S, Fukuda T et al. 2016. Genotype-directed dosing leads to optimized voriconazole levels in pediatric patients receiving hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 22:3482–86
    [Google Scholar]
  106. 106. 
    Wagner JB, Abdel-Rahman S, Van Haandel L, Gaedigk A, Gaedigk R et al. 2018. Impact of SLCO1B1 genotype on pediatric simvastatin acid pharmacokinetics. J. Clin. Pharmacol. 58:6823–33
    [Google Scholar]
  107. 107. 
    Aka I, Bernal CJ, Carroll R, Maxwell-Horn A, Oshikoya KA, Van Driest SL 2017. Clinical pharmacogenetics of cytochrome P450-associated drugs in children. J. Pers. Med. 7:414
    [Google Scholar]
  108. 108. 
    Chai G, Governale L, McMahon AW, Trinidad JP, Staffa J, Murphy D 2012. Trends of outpatient prescription drug utilization in US children, 2002–2010. Pediatrics 130:123–31
    [Google Scholar]
  109. 109. 
    Marsh S, Xiao M, Yu J, Ahluwalia R, Minton M et al. 2004. Pharmacogenomic assessment of carboxylesterases 1 and 2. Genomics 84:4661–68
    [Google Scholar]
  110. 110. 
    Zhu H-J, Patrick KS, Yuan H-J, Wang J-S, Donovan JL et al. 2008. Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am. J. Hum. Genet. 82:61241–48
    [Google Scholar]
  111. 111. 
    Nemoda Z, Angyal N, Tarnok Z, Gadoros J, Sasvari-Szekely M 2009. Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD. Neuropharmacology 57:7–8731–33
    [Google Scholar]
  112. 112. 
    Stage C, Jürgens G, Guski LS, Thomsen R, Bjerre D et al. 2017. The impact of CES1 genotypes on the pharmacokinetics of methylphenidate in healthy Danish subjects. Br. J. Clin. Pharmacol. 83:71506–14
    [Google Scholar]
  113. 113. 
    Youngster I, Zachor DA, Gabis LV, Bar-Chaim A, Benveniste-Levkovitz P et al. 2014. CYP2D6 genotyping in paediatric patients with autism treated with risperidone: a preliminary cohort study. Dev. Med. Child Neurol. 56:10990–94
    [Google Scholar]
  114. 114. 
    Nussbaum LA, Dumitraşcu V, Tudor A, Grădinaru R, Andreescu N, Puiu M 2014. Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype. Rom. J. Morphol. Embryol. 55:3877–84
    [Google Scholar]
  115. 115. 
    dos Santos A Jr, Henriques TB, de Mello MP, Ferreira Neto AP, Paes LA et al. 2015. Hyperprolactinemia in children and adolescents with use of risperidone: clinical and molecular genetics aspects. J. Child Adolesc. Psychopharmacol. 25:10738–48
    [Google Scholar]
  116. 116. 
    Oshikoya KA, Neely KM, Carroll RJ, Aka IT, Maxwell-Horn AC et al. 2019. CYP2D6 genotype and adverse events to risperidone in children and adolescents. Pediatr. Res. 85:5602–6
    [Google Scholar]
  117. 117. 
    Ward RM, Kearns GL. 2013. Proton pump inhibitors in pediatrics: mechanism of action, pharmacokinetics, pharmacogenetics, and pharmacodynamics. Pediatr. Drugs 15:2119–31
    [Google Scholar]
  118. 118. 
    Kearns GL, Blumer J, Schexnayder S, James LP, Adcock KG et al. 2008. Single-dose pharmacokinetics of oral and intravenous pantoprazole in children and adolescents. J. Clin. Pharmacol. 48:111356–65
    [Google Scholar]
  119. 119. 
    Kearns GL, Leeder JS, Gaedigk A 2010. Impact of the CYP2C19*17 allele on the pharmacokinetics of omeprazole and pantoprazole in children: evidence for a differential effect. Drug Metab. Dispos. 38:6894–97
    [Google Scholar]
  120. 120. 
    Gumus E, Karaca O, Babaoglu MO, Baysoy G, Balamtekin N et al. 2012. Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype-phenotype correlation in childhood. Eur. J. Clin. Pharmacol. 68:5629–36
    [Google Scholar]
  121. 121. 
    Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN et al. 2018. Obese children require lower doses of pantoprazole than nonobese peers to achieve equal systemic drug exposures. J. Pediatr. 193:102–8.e1
    [Google Scholar]
  122. 122. 
    Lima JJ, Lang JE, Mougey EB, Blake KB, Gong Y et al. 2013. Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J. Pediatr. 163:3686–91
    [Google Scholar]
  123. 123. 
    Lang JE, Holbrook JT, Mougey EB, Wei CY, Wise RA et al. 2015. Lansoprazole is associated with worsening asthma control in children with the CYP2C19 poor metabolizer phenotype. Ann. Am. Thorac. Soc. 12:6878–85
    [Google Scholar]
  124. 124. 
    Franciosi JP, Mougey EB, Williams A, Gomez-Suarez RA, Thomas C et al. 2018. Association between CYP2C19*17 alleles and pH probe testing outcomes in children with symptomatic gastroesophageal reflux. J. Clin. Pharmacol. 58:189–96
    [Google Scholar]
  125. 125. 
    Franciosi JP, Mougey EB, Williams A, Gomez Suarez RA, Thomas C et al. 2018. Association between CYP2C19 extensive metabolizer phenotype and childhood anti-reflux surgery following failed proton pump inhibitor medication treatment. Eur. J. Pediatr. 177:169–77
    [Google Scholar]
  126. 126. 
    Molina-Infante J, Rodriguez-Sanchez J, Martinek J, van Rhijn BD, Krajciova J et al. 2015. Long-term loss of response in proton pump inhibitor-responsive esophageal eosinophilia is uncommon and influenced by CYP2C19 genotype and rhinoconjunctivitis. Am. J. Gastroenterol. 110:111567–75
    [Google Scholar]
  127. 127. 
    Price Evans DA, Manley KA, McKusick VA 1960. Genetic control of isoniazid metabolism in man. Br. Med. J. 2:5197485–91
    [Google Scholar]
  128. 128. 
    Evans FT, Gray PWS, Lehmann H, Silk E 1952. Sensitivity to succinylcholine in relation to serum-cholinesterase. Lancet 1:67211229–30
    [Google Scholar]
  129. 129. 
    Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL 1977. Polymorphic hydroxylation of Debrisoquine in man. Lancet 2:8038584–86
    [Google Scholar]
  130. 130. 
    Van Driest SL, Choi L 2019. Real world data for pediatric pharmacometrics: Can we upcycle clinical data for research use. ? Clin. Pharmacol. Ther. 106:18486
    [Google Scholar]
  131. 131. 
    Lee CR, Sriramoju VB, Cervantes A, Howell LA, Varunok N et al. 2018. Clinical outcomes and sustainability of using CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. Circ. Genom. Precis. Med. 11:4e002069
    [Google Scholar]
  132. 132. 
    Williams AK, Klein MD, Martin J, Weck KE, Rossi JS et al. 2019. CYP2C19 genotype-guided antiplatelet therapy and 30-day outcomes after percutaneous coronary intervention. Circ. Genom. Precis. Med. 12:2e002441
    [Google Scholar]
  133. 133. 
    Empey PE, Stevenson JM, Tuteja S, Weitzel KW, Angiolillo DJ et al. 2018. Multisite investigation of strategies for the implementation of CYP2C19 genotype-guided antiplatelet therapy. Clin. Pharmacol. Ther. 104:4664–74
    [Google Scholar]
  134. 134. 
    Bell GC, Crews KR, Wilkinson MR, Haidar CE, Hicks JK et al. 2013. Development and use of active clinical decision support for preemptive pharmacogenomics. J. Am. Med. Inform. Assoc. 21:e1e93–99
    [Google Scholar]
  135. 135. 
    Bielinski SJ, Olson JE, Pathak J, Weinshilboum RM, Wang L et al. 2014. Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time—using genomic data to individualize treatment protocol. Mayo Clin. Proc. 89:125–33
    [Google Scholar]
  136. 136. 
    Danahey K, Borden BA, Furner B, Yukman P, Hussain S et al. 2017. Simplifying the use of pharmacogenomics in clinical practice: building the genomic prescribing system. J. Biomed. Inform. 75:110–21
    [Google Scholar]
  137. 137. 
    Leeder JS, Brown JT, Soden SE 2014. Individualizing the use of medications in children: making Goldilocks happy. Clin. Pharmacol. Ther. 96:3304–6
    [Google Scholar]
  138. 138. 
    Manzi SF, Fusaro VA, Chadwick L, Brownstein C, Clinton C et al. 2017. Creating a scalable clinical pharmacogenomics service with automated interpretation and medical record result integration—experience from a pediatric tertiary care facility. J. Am. Med. Inform. Assoc. 24:174–80
    [Google Scholar]
  139. 139. 
    Traynor K. 2019. CPIC secures $5 million for pharmacogenetics work. Am. J. Health. Syst. Pharm. 76:4197
    [Google Scholar]
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