The c.480C>G polymorphism of hOCT1 influences imatinib clearance in patients affected by chronic myeloid leukemia

被引：0

作者：

A Di Paolo

M Polillo

M Capecchi

G Cervetti

C Baratè

S Angelini

F Guerrini

G Fontanelli

R Arici

E Ciabatti

S Grassi

G Bocci

P Hrelia

R Danesi

M Petrini

S Galimberti

机构：

[1] University of Pisa,Department of Clinical and Experimental Medicine

[2] Via Roma 55,Department of Pharmacy and Biotechnology

[3] Pisa,undefined

[4] Italy,undefined

[5] University of Bologna,undefined

[6] Via Irnerio 48,undefined

[7] Bologna,undefined

[8] Italy,undefined

[9] Istituto Toscano Tumori,undefined

[10] Via Alderotti 86/N,undefined

[11] Florence,undefined

[12] Italy,undefined

来源：

The Pharmacogenomics Journal | 2014年 / 14卷

关键词：

chronic myeloid leukemia; hOCT1; imatinib; pharmacogenetics; pharmacokinetics;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

The aim of the study was to investigate any possible influence of polymorphisms of transmembrane transporters human organic cation transporter 1 (hOCT1), ABCB1, ABCG2 on imatinib pharmacokinetics in 33 men and 27 women (median age and range, 56 and 27–79 years, respectively) affected by chronic myeloid leukemia. A population pharmacokinetic analysis was performed to investigate imatinib disposition in every patient and the role of transporter polymorphisms. Results showed that the α1-acid glycoprotein and the c.480C>G genotype of hOCT1 had a significant effect on apparent drug clearance (CL/F) being responsible, respectively, for a 20% and 10% decrease in interindividual variability (IIV) of CL/F (from 50.1 up to 19.6%). Interestingly, 25 patients carrying at least one polymorphic c.480 G allele had a significant lower CL/F value with respect to the 35 c.480CC individuals (mean±s.d., 9.6±1.6 vs 12.1±2.3 l h−1, respectively; P<0.001). In conclusion, the hOCT1 c.480C>G SNP may significantly influence imatinib pharmacokinetics, supporting further analyses in larger groups of patients.

引用

页码：328 / 335

页数：7

共 152 条

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