Possible role of CYP2B6 genetic polymorphisms in ifosfamide-induced encephalopathy: report of three cases
| Autor: | Jeremy Bellien, Céline Verstuyft, Bruno Filhon, Thomas Duflot, Fabien Lamoureux, Robinson Joannides, Tony Pereira, Nathalie Massy-Guillemant, Aude Marie-Cardine |
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| Přispěvatelé: | UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Charles Nicolle [Rouen], CHU Rouen, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Barrière et passage des médicaments, Université Paris-Sud - Paris 11 (UP11)-IFR141, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), TAN, Yossan-Var |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
CYP2B6
[SDV.IMM] Life Sciences [q-bio]/Immunology [SDV]Life Sciences [q-bio] Encephalopathy Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine parasitic diseases Genotype medicine Pharmacology (medical) Allele Genotyping ComputingMilieux_MISCELLANEOUS Ifosfamide CYP3A4 business.industry bacterial infections and mycoses medicine.disease 3. Good health [SDV] Life Sciences [q-bio] 030220 oncology & carcinogenesis [SDV.IMM]Life Sciences [q-bio]/Immunology business Pharmacogenetics medicine.drug |
| Zdroj: | Fundamental & Clinical Pharmacology Fundamental & Clinical Pharmacology, 2018, 32 (3), pp.337-342. ⟨10.1111/fcp.12345⟩ Fundamental and Clinical Pharmacology Fundamental and Clinical Pharmacology, Wiley, 2018, 32 (3), pp.337-342. ⟨10.1111/fcp.12345⟩ |
| ISSN: | 0767-3981 1472-8206 |
| DOI: | 10.1111/fcp.12345⟩ |
| Popis: | Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In three consecutive cases of pediatric patients who exhibited IFA-induced encephalopathy (IIE), genotyping of clinically relevant single-nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed. Genetic investigations revealed the presence of CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6 allelic variant. All patients carried CYP3A4 wild-type genotype (CYP3A4*1/*1). Because CYP2B6-deficient alleles may be responsible for an increased conversion of S-IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help to avoid IIE and improve clinical outcomes. |
| Databáze: | OpenAIRE |
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