Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.

CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

See all formats and pricing
More options …
Volume 31, Issue 1


Clinical implementation of pharmacogenetics

Xandra García-González
  • Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Teresa Cabaleiro
  • Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
  • Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ María José Herrero
  • Hospital Universitario y Politécnico La Fe, Instituto de Incvestigación Sanitaria La Fe, Valencia, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Howard McLeod / Luis A. López-Fernández
  • Corresponding author
  • Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Doctor Esquerdo 46, 28007 Madrid, Spain
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-01-09 | DOI: https://doi.org/10.1515/dmpt-2015-0031


In the last decade, pharmacogenetic research has been performed in different fields. However, the application of pharmacogenetic findings to clinical practice has not been as fast as desirable. The current situation of clinical implementation of pharmacogenetics is discussed. This review focuses on the advances of pharmacogenomics to individualize cancer treatments, the relationship between pharmacogenetics and pharmacodynamics in the clinical course of transplant patients receiving a combination of immunosuppressive therapy, the needs and barriers facing pharmacogenetic clinical application, and the situation of pharmacogenetic testing in Spain. It is based on lectures presented by speakers of the Clinical Implementation of Pharmacogenetics Symposium at the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held in April 20, 2015.

Keywords: biomarkers; clinical implementation; genetic tests; pharmacogenetics; polymorphisms


  • 1.

    Crews KR, Hicks JK, Pui C-H, Relling MV, Evans WE. Pharmacogenomics and individualized medicine: translating science into practice. Clin Pharmacol Ther 2012;92:467–75.Google Scholar

  • 2.

    Bank PC, Swen JJ, Guchelaar H-J. Pharmacogenetic biomarkers for predicting drug response. Expert Rev Mol Diagn 2014;14:723–35.CrossrefGoogle Scholar

  • 3.

    Horgan D, Jansen M, Leyens L, Lal JA, Sudbrak R, Hackenitz E, et al. An index of barriers for the implementation of personalised medicine and pharmacogenomics in Europe. Public Health Genomics 2014;17:287–98.CrossrefGoogle Scholar

  • 4.

    Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, et al. Pharmacogenetics: from bench to byte – an update of guidelines. Clin Pharmacol Ther 2011;89:662–73.CrossrefGoogle Scholar

  • 5.

    Rodríguez-Antona C, Taron M. Pharmacogenomic biomarkers for personalized cancer treatment. J Intern Med 2015;277: 201–17.CrossrefGoogle Scholar

  • 6.

    McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, et al. Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol 2010;28:3227–33.CrossrefGoogle Scholar

  • 7.

    Pirmohamed M. Personalized pharmacogenomics: predicting efficacy and adverse drug reactions. Annu Rev Genomics Hum Genet 2014;15:349–70.CrossrefGoogle Scholar

  • 8.

    Provenzani A, Santeusanio A, Mathis E, Notarbartolo M, Labbozzetta M, Poma P, et al. Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients. World J Gastroenterol 2013;19:9156–73.CrossrefGoogle Scholar

  • 9.

    Quaglia M, Terrazzino S, Boldorini R, Stratta P, Genazzani AA. Severe acute nephrotoxicity in a kidney transplant patient despite low tacrolimus levels: a possible interaction between donor and recipient genetic polymorphisms. J Clin Pharm Ther 2013;38:333–6.CrossrefGoogle Scholar

  • 10.

    Mok T, Wu Y-L, Lee JS, Yu C-J, Sriuranpong V, Sandoval-Tan J, et al. Detection and dynamic changes of EGFR mutations from circulating tumor DNA as a predictor of survival outcomes in NSCLC patients treated with first-line intercalated erlotinib and chemotherapy. Clin Cancer Res 2015;21:3196–203.CrossrefGoogle Scholar

  • 11.

    McLeod HL. Cancer pharmacogenomics: early promise, but concerted effort needed. Science 2013;339:1563–6.CrossrefGoogle Scholar

  • 12.

    McWhinney-Glass S, Winham SJ, Hertz DL, Yen Revollo J, Paul J, He Y, et al. Cumulative genetic risk predicts platinum/taxane-induced neurotoxicity. Clin Cancer Res 2013;19:5769–76.CrossrefGoogle Scholar

  • 13.

    Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. N Engl J Med 2011;364:1144–53.CrossrefGoogle Scholar

  • 14.

    Hertz DL, Roy S, Jack J, Motsinger-Reif AA, Drobish A, Clark LS, et al. Genetic heterogeneity beyond CYP2C8*3 does not explain differential sensitivity to paclitaxel-induced neuropathy. Breast Cancer Res Treat 2014;145:245–54.Google Scholar

  • 15.

    Hariani GD, Lam ET, Lam EJ, Havener T, Kwok P-Y, McLeod HL, et al. Application of next generation sequencing to CEPH cell lines to discover variants associated with FDA approved chemotherapeutics. BMC Res Notes 2014;7:360.CrossrefGoogle Scholar

  • 16.

    Fachal L, Gómez-Caamaño A, Barnett GC, Peleteiro P, Carballo AM, Calvo-Crespo P, et al. A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. Nat Genet 2014;46:891–4.CrossrefGoogle Scholar

  • 17.

    Goff LW, Thakkar N, Du L, Chan E, Tan BR, Cardin DB, et al. Thymidylate synthase genotype-directed chemotherapy for patients with gastric and gastroesophageal junction cancers. PLoS One 2014;9:e107424.CrossrefGoogle Scholar

  • 18.

    Kelly CM, Pritchard KI. Personalized medicine: what exactly is it and can we truly measure it? J Clin Oncol 2012;30:2173–4.CrossrefGoogle Scholar

  • 19.

    Ramos EM, Din-Lovinescu C, Berg JS, Brooks LD, Duncanson A, Dunn M, et al. Characterizing genetic variants for clinical action. Am J Med Genet C Semin Med Genet 2014;166C:93–104.Google Scholar

  • 20.

    Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ. An open-label, concentration-ranging trial of FK506 in primary kidney transplantation: a report of the United States Multicenter FK506 Kidney Transplant Group. Transplantation 1996;62:900–5.CrossrefGoogle Scholar

  • 21.

    Venkataramanan R, Shaw LM, Sarkozi L, Mullins R, Pirsch J, MacFarlane G, et al. Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients. J Clin Pharmacol 2001;41:542–51.CrossrefGoogle Scholar

  • 22.

    Brunet M, Campistol JM, Diekmann F, Guillen D, Millán O. T-cell function monitoring in stable renal transplant patients treated with sirolimus monotherapy. Mol Diagn Ther 2007;11:247–56.CrossrefGoogle Scholar

  • 23.

    Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet 2004;43:623–53.CrossrefGoogle Scholar

  • 24.

    Picard N, Marquet P. The influence of pharmacogenetics and cofactors on clinical outcomes in kidney transplantation. Expert Opin Drug Metab Toxicol 2011;7:731–43.Google Scholar

  • 25.

    Haufroid V, Mourad M, Van Kerckhove V, Wawrzyniak J, De Meyer M, Eddour DC, et al. The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 2004;14:147–54.CrossrefGoogle Scholar

  • 26.

    Wallemacq P, Armstrong VW, Brunet M, Haufroid V, Holt DW, Johnston A, et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 2009;31:139–52.CrossrefGoogle Scholar

  • 27.

    Gómez-Bravo MA, Salcedo M, Fondevila C, Suarez F, Castellote J, Rufian S, et al. Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in Caucasian Spanish liver transplant patients. J Clin Pharmacol 2013;53:1146–54.Google Scholar

  • 28.

    Mourad M, Wallemacq P, De Meyer M, Malaise J, De Pauw L, Eddour DC, et al. Biotransformation enzymes and drug transporters pharmacogenetics in relation to immunosuppressive drugs: impact on pharmacokinetics and clinical outcome. Transplantation 2008;85:S19–24.CrossrefGoogle Scholar

  • 29.

    Hesselink DA, van Schaik RH, van Agteren M, de Fijter JW, Hartmann A, Zeier M, et al. CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients. Pharmacogenet Genomics 2008;18:339–48.CrossrefGoogle Scholar

  • 30.

    Thervet E, Loriot MA, Barbier S, Buchler M, Ficheux M, Choukroun G, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther 2010;87:721–6.Google Scholar

  • 31.

    Van Gelder T, Hesselink DA. Dosing tacrolimus based on CYP3A5 genotype: will it improve clinical outcome? Clin Pharmacol Ther 2010;87:640–1.CrossrefGoogle Scholar

  • 32.

    Quteineh L, Verstuyft C. Pharmacogenetics in immunosuppressants: impact on dose requirement of calcineurin inhibitors in renal and liver pediatric transplant recipients. Curr Opin Organ Transplant 2010;15:601–7.CrossrefGoogle Scholar

  • 33.

    Li L, Li C-J, Zheng L, Zhang Y-J, Jiang H-X, Si-Tu B, et al. Tacrolimus dosing in Chinese renal transplant recipients: a population-based pharmacogenetics study. Eur J Clin Pharmacol 2011;67:787–95.CrossrefGoogle Scholar

  • 34.

    Rahsaz M, Azarpira N, Nikeghbalian S, Aghdaie MH, Geramizadeh B, Moini M, et al. Association between tacrolimus concentration and genetic polymorphisms of CYP3A5 and ABCB1 during the early stage after liver transplant in an Iranian population. Exp Clin Transplant 2012;10:24–9.CrossrefGoogle Scholar

  • 35.

    Hauser IA, Schaeffeler E, Gauer S, Scheuermann EH, Wegner B, Gossmann J, et al. ABCB1 genotype of the donor but not of the recipient is a major risk factor for cyclosporine-related nephrotoxicity after renal transplantation. J Am Soc Nephrol 2005;16:1501–11.CrossrefGoogle Scholar

  • 36.

    Woillard J-B, Rerolle J-P, Picard N, Rousseau A, Guillaudeau A, Munteanu E, et al. Donor P-gp polymorphisms strongly influence renal function and graft loss in a cohort of renal transplant recipients on cyclosporine therapy in a long-term follow-up. Clin Pharmacol Ther 2010;88:95–100.CrossrefGoogle Scholar

  • 37.

    Lv R, Hu X, Bai Y, Long H, Xu L, Liu Z, et al. Association between IL-6-174G/C polymorphism and acute rejection of renal allograft: evidence from a meta-analysis. Transpl Immunol 2012;26:11–8.Google Scholar

  • 38.

    Hu X, Bai Y, Li S, Zeng K, Xu L, Liu Z, et al. Donor or recipient TNF-A-308G/A polymorphism and acute rejection of renal allograft: a meta-analysis. Transpl Immunol 2011;25:61–71.CrossrefGoogle Scholar

  • 39.

    Hwang Y-H, Ro H, Choi I, Kim H, Oh K-H, Hwang J-I, et al. Impact of polymorphisms of TLR4/CD14 and TLR3 on acute rejection in kidney transplantation. Transplantation 2009;88:699–705.CrossrefGoogle Scholar

  • 40.

    Singh R, Manchanda PK, Kesarwani P, Srivastava A, Mittal RD. Influence of genetic polymorphisms in GSTM1, GSTM3, GSTT1 and GSTP1 on allograft outcome in renal transplant recipients. Clin Transplant 2009;23:490–8.Google Scholar

  • 41.

    Lloberas N, Torras J, Cruzado JM, Andreu F, Oppenheimer F, Sánchez-Plumed J, et al. Influence of MRP2 on MPA pharmacokinetics in renal transplant recipients-results of the Pharmacogenomic Substudy within the Symphony Study. Nephrol Dial Transplant 2011;26:3784–93.CrossrefGoogle Scholar

  • 42.

    Brunet M, Millán O, Martorell J. Donor-recipient genetic diversity: the role of pharmacogenomics in kidney transplantation. Pharmacogenomics 2013;14:1369–72.CrossrefGoogle Scholar

  • 43.

    Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012;12:388–99.CrossrefGoogle Scholar

  • 44.

    Green ED, Guyer MS. Charting a course for genomic medicine from base pairs to bedside. Nature 2011;470:204–13.CrossrefGoogle Scholar

  • 45.

    Pirmohamed M. Acceptance of biomarker-based tests for application in clinical practice: criteria and obstacles. Clin Pharmacol Ther 2010;88:862–6.CrossrefGoogle Scholar

  • 46.

    Scott SA. Personalizing medicine with clinical pharmacogenetics. Genet Med 2011;13:987–95.CrossrefGoogle Scholar

  • 47.

    Johnson DR, Galanis E. Incorporation of prognostic and predictive factors into glioma clinical trials. Curr Oncol Rep 2013;15:56–63.CrossrefGoogle Scholar

  • 48.

    Overby CL, Tarczy-Hornoch P. Personalized medicine: challenges and opportunities for translational bioinformatics. Per Med 2013;10:453–62.CrossrefGoogle Scholar

  • 49.

    Filipski KK, Mechanic LE, Long R, Freedman AN. Pharmacogenomics in oncology care. Front Genet 2014;5:73.CrossrefGoogle Scholar

  • 50.

    Bozic I, Reiter JG, Allen B, Antal T, Chatterjee K, Shah P, et al. Evolutionary dynamics of cancer in response to targeted combination therapy. Elife 2013;2013:1–15.Google Scholar

  • 51.

    Gutiérrez C, Rodriguez J, Patiño-García A, García-Foncillas J, Salgado J. KRAS mutational status analysis of peripheral blood isolated circulating tumor cells in metastatic colorectal patients. Oncol Lett 2013;6:1343–5.Google Scholar

  • 52.

    Manterola L, Guruceaga E, Gállego Pérez-Larraya J, González-Huarriz M, Jauregui P, Tejada S, et al. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro Oncol 2014;16:520–7.CrossrefGoogle Scholar

  • 53.

    Dressler LG, Deal AM, Patel J, Markey J, Van RM, McLeod HL. Personalized medicine. Per Med 2014;11:143–53.CrossrefGoogle Scholar

  • 54.

    Weinshilboum R, Wang L. Pharmacogenomics: bench to bedside. Nat Rev Drug Discov 2004;3:739–48.CrossrefGoogle Scholar

  • 55.

    Food and Drug Administration. Genomics – table of pharmacogenomic biomarkers in drug labeling. Center for Drug Evaluation and Research. Available at: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm. Accessed: 26 Aug 2015.

  • 56.

    European Medicines Agency. European Medicines Agency – multidisciplinary: pharmacogenomics. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000411.jsp&mid=WC0b01ac058002958e. Accessed: 26 Aug 2015.

  • 57.

    PharmGKB-CPIC. List Dosing Guidelines [Internet]. Available at: https://www.pharmgkb.org/view/dosing-guidelines.do?source=CPIC#. Accessed: 26 Aug 2015.

  • 58.

    Pharmacogénéticque.fr. Accueil – pharmacologie faculté de médecine Paris Sud. Available at: http://www.pharmacogenetics.fr/. Accessed: 26 Aug 2015.

  • 59.

    Becquemont L, Alfirevic A, Amstutz U, Brauch H, Jacqz-Aigrain E, Laurent-Puig P, et al. Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics 2011;12:113–24.CrossrefGoogle Scholar

  • 60.

    Pharmacogenomics SEFF – Sociedad Española de Farmacogenética y Farmacogenómica. Available at: http://www.seff.es/doc2.php?op=buscar_labs. Accessed: 26 Aug 2015.

About the article

Corresponding author: Luis A. López-Fernández, Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Doctor Esquerdo 46, 28007 Madrid, Spain, E-mail:

aXandra García-González, Teresa Cabaleiro and María José Herrero contributed equally to this work.

Received: 2015-08-26

Accepted: 2015-11-20

Published Online: 2016-01-09

Published in Print: 2016-03-01

Citation Information: Drug Metabolism and Personalized Therapy, Volume 31, Issue 1, Pages 9–16, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2015-0031.

Export Citation

©2016 by De Gruyter.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Danielle Johnson, Dyfrig Hughes, Sir Munir Pirmohamed, and Andrea Jorgensen
Journal of Personalized Medicine, 2019, Volume 9, Number 3, Page 42
Luis A. López-Fernández
Journal of Personalized Medicine, 2018, Volume 8, Number 4, Page 40
Natasa Djordjevic, Stefania Boccia, and Róza Ádány
Frontiers in Public Health, 2018, Volume 6

Comments (0)

Please log in or register to comment.
Log in