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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1.
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Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1.

机译：紫杉醇在卵巢癌患者中的药代动力学和CYP2C8，CYP3A4和MDR1的遗传多态性。

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摘要

Interindividual differences in the pharmacokinetics of paclitaxel and its metabolites in Japanese ovarian cancer patients were investigated in relation to genetic polymorphisms of the CYP2C8, CYP3A4, and MDR1 genes. The area under the concentration-time curve (AUC) ratios of paclitaxel/6alpha-hydroxypaclitaxel and paclitaxel/3 -p-hydroxypaclitaxel calculated as the metabolic index of CYP2C8 and CYP3A4 showed 13- and 12-fold interindividual variations, respectively. No patient had any CYP2C8 variants, while 2 patients were heterozygotes of CYP3A4*16. For the MDR1 gene, the frequencies of -129C, 1236C, 2677T, 2677A, and 3435T alleles were 2.2%, 8.7%, 56.5%, 4.4%, and 52.2%, respectively. Subjects possessing the 3435T allele had a significantly (P < .05) higher AUC of 3'- p-hydroxypaclitaxel compared to those possessing the 3435C allele. Leukocytopenia was significantly (P < .05) related to the AUC of paclitaxel. Genotyping of the CYP2C8, CYP3A4, and MDR1 genes might not be essential to predict adverse effects of paclitaxel in Japanese patients, although an allelic variant of MDR1 may functionally affect the pharmacokinetics of its metabolite.
机译：研究了日本卵巢癌患者中紫杉醇及其代谢产物的药代动力学的个体差异与CYP2C8，CYP3A4和MDR1基因的遗传多态性的关系。以CYP2C8和CYP3A4的代谢指数计算的紫杉醇/6α-羟基紫杉醇和紫杉醇/ 3-对羟基紫杉醇的浓度-时间曲线（AUC）比下的面积分别显示出13倍和12倍的个体差异。没有患者有任何CYP2C8变异体，而2名患者为CYP3A4 * 16杂合子。对于MDR1基因，-129C，1236C，2677T，2677A和3435T等位基因的频率分别为2.2％，8.7％，56.5％，4.4％和52.2％。与拥有3435C等位基因的受试者相比，拥有3435T等位基因的受试者的3'-对羟基紫杉醇的AUC显着更高（P <0.05）。白细胞减少症与紫杉醇的AUC显着相关（P <.05）。 CYP2C8，CYP3A4和MDR1基因的基因分型对于预测紫杉醇对日本患者的不良反应可能不是必不可少的，尽管MDR1的等位基因变体可能在功能上影响其代谢物的药代动力学。

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