与正常体重个体相比,在胃绕道或严格饮食之前和之后患有肥胖症的患者的迪戈辛药理学

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Kine Eide Kvitne¹, Markus Hovd², Line Kristin Johnson³

¹Department of Pharmacy, University of Oslo, Blindern, P.O. Box 1068, 0316, Oslo, Norway. k.e.kvitne@farmasi.uio.no.

Clinical pharmacokinetics

|November 22, 2023

概括

通过Roux-en-Y胃绕道 (RYGB) 或饮食减肥对迪戈辛的药理动力学影响很小,这表明P-糖蛋白 (P-gp) 活性变化没有临床意义. 肥胖患者的迪戈辛暴露率较低,可能是由于肝脏P-gp表达率较高.

科学领域:

药理动力学药理动力学
药物新陈代谢药物新陈代谢
肥胖问题研究研究

背景情况:

P-glycoprotein (P-gp) 输出输送器影响屏障组织中的药物吸收.
肥胖,体重减轻和Roux-en-Y胃绕道 (RYGB) 可能会改变P-gp活性和药物反应的可变性.

研究的目的:

作为P-gp表型指标,研究狄戈辛的药理动力学.
在减肥前和减肥后 (RYGB或饮食) 肥胖患者的P-gp活性与正常体重个体进行比较.

主要方法:

包括接受RYGB (n=40) 或饮食 (n=40) 的严重肥胖患者,以及正常体重对照 (n=18).
在2年多的多个时间点进行的药理动力学研究中使用狄戈辛.
通过手术患者的活检评估肝脏和骨P-gp水平.

主要成果:

减肥组在9周内显示了可比的体重减轻和轻微 (<16%) 的狄戈辛AUC增加.
在RYGB患者中,手术后达到最大度的时间减少.
与对照组相比,肥胖患者的基线迪戈辛AUC较低 (-26%) 和RYGB患者的肝脏P-gp水平较高 (+29%).

结论:

通过饮食或RYGB诱导的体重减轻或临床上无意义的迪戈辛药理学变化.
肥胖患者较低的狄戈辛暴露表明胆道分泌量增加,可能是由于肝脏P-gp表达率较高.

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