在接受乳腺癌治疗的绝经后妇女中,肠道P-gp活性降低
Joao Paulo B Ximenez1, Jurandyr Moreira de Andrade2, Adriana Rocha1
1School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Clinical and translational science
|January 16, 2024
概括
更年期状态显著影响肠道P-glycoprotein (P-gp) 的活性. 绝经后妇女的P-gp功能减少,导致P-gp基质的口服药物生物可用性增加.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物新陈代谢 药物新陈代谢
- 临床药理动力学 临床药理动力学
背景情况:
- 肠道P-糖蛋白 (P-gp) 活性影响口服药物的生物可用性.
- 与怀孕相关的荷尔蒙在体外上调P-gp.
- 更年期状态是影响P-gp活性的一个潜在因素.
研究的目的:
- 为了研究更年期状态对肠道P-gp活性的影响.
- 在绝经前和绝经后妇女中评估fexofenadine的药理动力学.
主要方法:
- 在绝经前 (n=20) 和绝经后 (n=20) 的乳腺癌患者中,在0-12小时内测量出fexofenadine的度.
- 通过液体染色学-并联质谱法进行量化.
- 使用多重线性回归分析曲线下的面积 (AUCinf) 和最大度 (Cmax).
主要成果:
- 与绝经前患者相比,绝经后患者的费克索芬纳丁Cmax和AUCinf显著更高.
- 携带ABCB1 3435 T等位基因的ABCB1 3435 T等位基因携带者比野生型个体的Cmax更高 (p=0.02).
- 在绝经后的个体中,P-gp活性估计下降40%.
结论:
- 更年期状态影响肠道P-gp活性,而在更年期后的妇女中观察到活性降低.
- 这种减少可能导致口服P-gp基质的血暴露增加.
- 遗传变异 (ABCB1 3435 T等位基因) 也可能影响P-gp活性和药物暴露.
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