Deferasirox pharmacogenetic influence on pharmacokinetic, efficacy and toxicity in a cohort of pediatric patients

被引：17

作者：

Allegra, Sarah ^{[1
]}

De Francia, Silvia ^{[2
]}

Cusato, Jessica ^{[1
]}

Arduino, Arianna ^{[1
]}

Massano, Davide ^{[2
]}

Longo, Filomena ^{[2
]}

Piga, Antonio ^{[2
]}

D 'Avolio, Antonio ^{[1
]}

机构：

[1] Univ Turin, Dept Med Sci, Unit Infect Dis, Amedeo Savoia Hosp, I-10149 Turin, Italy

[2] Univ Turin, S Luigi Gonzaga Hosp, Dept Biol & Clin Sci, I-10043 Orbassano, TO, Italy

来源：

PHARMACOGENOMICS | 2017年 / 18卷 / 06期

关键词：

beta-thalassemia; BCRP1; creatinine; CYP1A1; CYP1A2; CYP2D6; ferritin; iron overload; LIC; SNP; DEPENDENT IRON OVERLOAD; GENETIC POLYMORPHISMS; BETA-THALASSEMIA; BREAST-CANCER; LINKAGE DISEQUILIBRIUM; COLORECTAL-CANCER; CHELATING THERAPY; LUNG-CANCER; CYP1A2; GENE; ABCG2;

D O I：

10.2217/pgs-2016-0176

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aim: We aimed to evaluate the influence of genetic polymorphisms involved in deferasirox metabolism and transport on its pharmacokinetics and treatment toxicity, in a cohort of beta-thalassaemic children. Patients & methods: Drug plasma concentrations were measured by a HPLC-UV method. Allelic discrimination for UGT1A1, UGT1A3, CYP1A1, CYP1A2, CYP2D6, MRP2 and BCRP1 polymorphisms was performed by realtime PCR. Results: CYP1A1 rs2606345AA influenced C-trough (p = 0.001) and t(1/2) (p = 0.042), CYP1A1 rs4646903TC/CC (p = 0.005) and BCRP1 rs2231142GA/AA (p = 0.005) influenced T-max and CYP2D6 rs1135840CG/GG influenced C-max (p = 0.044). UGT1A1 rs887829TT (p = 0.002) and CYP1A2 rs762551CC (p = 0.019) resulted as predictive factor of ferritin levels and CYP1A1 rs2606345CA/AA (p = 0.021) and CYP1A2 rs762551AC/CC (p = 0.027) of liver iron concentration. Conclusion: Our data suggest the usefulness of deferasirox pharmacogenetics in pediatric treatment optimization.

引用

页码：539 / 554

页数：16

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