Case report : Hepatotoxicity and nephrotoxicity induced by methotrexate in a paediatric patient, what is the role of precision medicine in 2023 ?

Article Article scientifique Rapport de cas Case report : Hepatotoxicity and nephrotoxicity induced by methotrexate in a paediatric patient, what is the role of precision medicine in 2023 ? eng 2023-05-02 2023 author El Rida El Masri Ali 0000-0002-9559-2445 Division of Clinical Pharmacology and Toxicology, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland. author Tobler Caroline Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland.,Cansearch Research Platform for Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 775417 author Willemijn Breunis Department of Oncology and Children's Research Center, Faculty of Medicine, University of Zurich, Zurich, Switzerland. author Von Bueren André 0000-0003-4197-6264 Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland.,Cansearch Research Platform for Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 885935 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Ansari Djaberi Marc Georges 0000-0002-9649-6498 Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland.,Cansearch Research Platform for Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 61572 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Samer Caroline Flora 0000-0001-8178-0616 Division of Clinical Pharmacology and Toxicology, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.,Department of Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 105661 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) 1130548 10.3389/fphar.2023.1130548 37201023 1663-9812 PMC10185764 https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1130548/full Methotrexate is an immunosuppressant and chemotherapeutic agent used in the treatment of a range of autoimmune disorders and cancers. Its main serious adverse effects, bone marrow suppression and gastrointestinal complications, arise from its antimetabolite effect. Nevertheless, hepatotoxicity and nephrotoxicity are two widely described adverse effects of methotrexate. Its hepatotoxicity has been studied mainly in the low-dose, chronic setting, where patients are at risk of fibrosis/cirrhosis. Studies of acute hepatoxicity of high dose methotrexate, such as during chemotherapy, are scarce. We present the case of a 14-year-old patient who received high-dose methotrexate and subsequently developed acute fulminant liver failure and acute kidney injury. Genotyping ofMTHFR(Methylene tetrahydrofolate reductase gene),ABCB1(codes for P-glycoprotein, intestinal transport and biliary excretion),ABCG2(codes for BCRP, intestinal transporter and renal excretion) andSLCO1B1(codes for OATP1B1, hepatic transporter) identified variants in all the genes analysed that predicted a reduced rate of methotrexate elimination and thus may have contributed to the clinical situation of the patient. Precision medicine involving pharmacogenomic testing could potentially avoid such adverse drug effects. Hepatotoxicity Nephrotoxicity Pediatric case report Pharmacogenomic Pharmacokinetic and pharmacodynamic parameters Dewey 617 Dewey 618 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 58 Département de pédiatrie, gynécologie et obstétrique 223 false 1280 Pharmaco-omiques et médecine de précision 1003 564 Oncologie et hématologie pédiatriques 907 Frontiers in pharmacology 14 fa05b256-5b6b-4dc1-9a1f-8a09869c1426 Article (Published version) Public Article-scientifique-from-europePmc.pdf 739907 application/pdf CC BY-4.0 5e6e21fc0f33919e18f7b2ee0d8d2251bb9c226894406c56911b35147e7f0dea openAccess Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Case report : Hepatotoxicity and nephrotoxicity induced by methotrexate in a paediatric patient, what is the role of precision medicine in 2023 ?	Frontiers in pharmacology			2023	122	253

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Tobler, Caroline