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在儿童中使用人口药理动力学方法评估与肥胖相关的Pantoprazole清除的生理变化
Tyler C Dunlap1, Daniel Gonzalez2,3, Kathryn E Kyler4,5
1Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
儿童肥胖与儿童的潘托普拉清除率 (CL) 降低18%有关. 这一发现突出了对肥胖青年药物剂量的潜在影响,需要进一步研究潜在的生理机制.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 儿科健康 儿科健康
- 代谢过程中的代谢.
背景情况:
- 儿童肥胖是一个全球性的健康问题,对药物疗效有重大影响.
- 与肥胖相关的生理变化可以改变药物药理动力学 (PK),但机制和剂量影响尚不清楚.
- 之前的观察表明,儿童肥胖症的潘托普拉清除率 (CL) 降低.
研究的目的:
- 为了研究儿童肥胖症中减少的潘托普拉CL.
- 探索与肥胖相关的肝脏生理学,作为改变 pantoprazole PK 的原因.
- 评估肥胖对潘托普拉药物剂量的临床相关性.
主要方法:
- 在6至21岁的肥胖和没有肥胖的儿童中进行前性,比较性PK研究.
- 非线性混合效应建模以确定潘托普拉PK的可变性.
- 蒙特卡洛模拟评估潘托普拉暴露和肥胖相关性.
主要成果:
- 研究包括39名儿科参与者 (69%患有肥胖症).
- 一个包含总体体重,CYP2C19表型和肥胖状况的两部分PK模型符合数据.
- 肥胖与潘托普拉CL的18%的降低有关,这与体重和CYP2C19状态无关.
结论:
- 肥胖与儿童患者的潘托普拉清除率降低独立相关.
- 观察到的CL的减少与CYP2C19功能丧失时观察到的减少相似.
- 需要进一步的研究来了解生理机制,并指导儿童肥胖症的药物剂量.
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