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首页> 外文期刊>Pharmacogenomics >Effects of pharmacogenetic variants on vemurafenib-related toxicities in patients with melanoma
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Effects of pharmacogenetic variants on vemurafenib-related toxicities in patients with melanoma

机译：药物发生变种对黑色素瘤患者vemurafenib相关毒性的影响

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Aim: The pharmacokinetics and pharmacodynamics of vemurafenib are characterized by a wide interpatient variability. Since multiple polymorphic enzymes and drug transporters are involved in vemurafenib pharmacokinetics, we studied associations of polymorphisms on vemurafenib-associated toxicities. Patients & methods: Prospectively collected samples of 97 melanoma patients treated with vemurafenib alone (n = 62) or in combination with cobimetinib (n = 35) were genotyped for ABCB1 (3435C>T), ABCG2 (421C>A, 34G>A) and CYP3A4 (*22, 15389C>T) polymorphisms. Associations between these variants and the incidence of toxicities were studied. Results:CYP3A4*22 was significantly associated with increased risk for grade >= 3 nausea, grade 1-4 hyperbilirubinemia, and cutaneous squamous cell carcinoma. ABCB1 3435C>T was a predictor for grade >= 3 toxicity. Conclusion: Genetic variants in CYP3A4 and ABCB1 are associated with vemurafenib-associated toxicities.
机译：目的：vemureafenib的药代动力学和药效学特征在于宽的内部间变异性。 由于多种多态性酶和药物转运蛋白涉及Vemureafenib药代动力学，因此我们研究了多态性对VemuRafenib相关毒性的关联。 患者和方法：单独使用vemureafenib（n = 62）或与cobimetinib（n = 35）治疗的97例黑色素瘤患者的预期收集的样品用于ABCB1（3435℃），ABCG2（42 1℃> A，34g> A）进行基因分型。 和CYP3A4（* 22,15389c> t）多态性。 研究了这些变体与毒性发病率之间的关联。 结果：CYP3A4 * 22显着与级别> = 3恶心，1-4级高胆红素血症和皮肤鳞状细胞癌的风险显着相关。 ABCB1 3435C> T是等级> = 3毒性的预测因子。 结论：CYP3A4和ABCB1中的遗传变异与VemuRafenib相关毒性有关。

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