Possible role of CYP2B6 genetic polymorphisms in ifosfamide-induced encephalopathy: report of three cases

被引：8

作者：

Duflot, Thomas ^{[1
,2
]}

Marie-Cardine, Aude ^{[3
]}

Verstuyft, Celine ^{[4
]}

Filhon, Bruno ^{[3
]}

Pereira, Tony ^{[1
]}

Massy-Guillemant, Nathalie ^{[1
]}

Joannides, Robinson ^{[1
,2
]}

Bellien, Jeremy ^{[1
,2
]}

Lamoureux, Fabien ^{[1
,2
]}

机构：

[1] Rouen Univ Hosp, Dept Pharmacol, 1 Rue Germont, F-76000 Rouen, France

[2] Rouen Univ, Normandie Univ, UNIROUEN, Inserm,U1096, 22 Blvd Gambetta, F-76000 Rouen, France

[3] Rouen Univ Hosp, Dept Pediat Hematol & Oncol, 1 Rue Germont, F-76000 Rouen, France

[4] CHU Bicetre, AP HP, Serv Genet Mol Pharmacogenet & Hormonol, 78 Rue Gen Leclerc, F-94275 Le Kremlin Bicetre, France

来源：

FUNDAMENTAL & CLINICAL PHARMACOLOGY | 2018年 / 32卷 / 03期

关键词：

CYP2B6; encephalopathy; ifosfamide metabolism; methylene blue; pharmacogenetics; RISK-FACTORS; METHYLENE-BLUE; METABOLISM; EFAVIRENZ; CANCER;

D O I：

10.1111/fcp.12345

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：337 / 342

页数：6

共 22 条

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