Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer
Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer
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DOI：
10.1038/tpj.2010.19
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发表时间：
2011-04-01
影响因子：
2.8
通讯作者：
Brosen, K.
中科院分区：
文献类型：
--
作者：
Bergmann, T. K.;Brasch-Andersen, C.;Brosen, K.
本研究的主要目的是评估CYP2C8*3和三种遗传ABCB1变异对紫杉醇消除的影响。我们研究了93名接受紫杉醇和卡铂治疗的高加索女性卵巢癌患者。采用稀疏采样和非线性混合效应模型，从血浆紫杉醇和cremoophor EL总量中估计未结合紫杉醇的个体清除率。间隙几何平均值为385 l h(-1)（范围为176 ~ 726 l h(-1)）。CYP2C8*3携带者清除率比非携带者低11%，P = 0.03。这在之前的类似研究中没有得到证实；解释可能是同时使用未结合紫杉醇清除率和同性患者群体的优势。ABCB1变异C1236T、G2677T/A和C3435T未发现显著关联。其次，对其他候选单核苷酸多态性进行了探索，发现CYP2C8*4 （P = 0.04）和ABCC1 G . 7356253c > G （P = 0.04）可能存在关联。The Pharmacogenomics Journal (2011) 11, 113-120；doi: 10.1038 / tpj.2010.19;2010年4月6日在线发布
The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h(-1) (range 176-726 l h(-1)). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P = 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P = 0.04) and ABCC1 g.7356253C > G (P = 0.04). The Pharmacogenomics Journal (2011) 11, 113-120; doi:10.1038/tpj.2010.19; published online 6 April 2010