Association of ABCB1 polymorphisms with erlotinib pharmacokinetics and toxicity in Japanese patients with non-small-cell lung cancer

被引：3

作者：

Hamada, Akinobu ^{[1
,2
]}

Sasaki, Ji-ichiro ^{[1
]}

Saeki, Sho ^{[2
]}

Iwamoto, Norihiro ^{[3
]}

Inaba, Megumi ^{[8
]}

Ushijima, Sunao ^{[8
]}

Urata, Maki ^{[4
]}

Kishi, Hiroto ^{[4
]}

Fujii, Shinji ^{[5
]}

Semba, Hiroshi ^{[5
]}

Kashiwabara, Kosuke ^{[6
]}

Tsubata, Yukari ^{[7
]}

Kai, Yuki ^{[2
]}

Isobe, Takeshi ^{[7
]}

Kohrogi, Hirotsugu ^{[2
]}

Saito, Hideyuki ^{[1
,2
]}

机构：

[1] Kumamoto Univ Hosp, Kumamoto, Japan

[2] Kumamoto Univ, Kumamoto, Japan

[3] Saiseikai Kumamoto Hosp, Kumamoto, Japan

[4] Kumamoto City Hosp, Kumamoto, Japan

[5] Kumamoto Reg Med Ctr, Kumamoto, Japan

[6] Kumamoto Med Ctr, Kumamoto, Japan

[7] Shimane Univ Hosp, Matsue, Shimane, Japan

[8] Kumamoto City Hosp, Kumamoto, Japan

来源：

PHARMACOGENOMICS | 2012年 / 13卷 / 05期

关键词：

ABCB1; erlotinib; Japanese; P-glycoprotein; pharmacokinetic; polymorphism; toxicity; TYROSINE KINASE INHIBITOR; P-GLYCOPROTEIN; GENETIC POLYMORPHISMS; MULTIDRUG-RESISTANCE; FUNCTIONAL POLYMORPHISMS; ANTIEPILEPTIC DRUGS; CLINICAL-RELEVANCE; TRANSPORTER ABCB1; SOLID TUMORS; IN-VIVO;

D O I：

10.2217/PGS.11.176

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aims: We analyzed the association of ABCB1 polymorphisms with erlotinib-induced toxicity and the pharmacokinetics in patients with non-small-cell lung cancer. Materials & methods: After erlotinib 150 mg was administered to 50 patients, ABCB1 polymorphisms were analyzed via either TaqMan (R) assays or direct nucleotide sequencing. Plasma concentrations were measured by HPLC. Results: The trough concentration at steady state in patients with the ABCB1 1236TT-2677TT-3435TT genotype was higher compared with others groups (p = 0.021) and patients carrying this genotype had a higher risk of developing higher grade 2 toxicity (p = 0.012). Conclusion: The present study suggested that the ABCB1 1236TT-2677TT-3435T1 genotype was associated with higher plasma concentration and the risk of developing higher toxicity in patients treated with erlotinib.

引用

页码：615 / 624

页数：10

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