Abstract:
The incidence of paediatric obesity continues to rise worldwide and contributes to a range of diseases including cardiovascular disease. Obesity in children has been shown to impact upon the plasma concentrations of various compounds, including amlodipine. Nonetheless, information on the influence of obesity on amlodipine pharmacokinetics and the need for dose adjustment has not been studied previously. This study applied the physiologically based pharmacokinetic modelling and established a paediatric obesity population to assess the impact of obesity on amlodipine pharmacokinetics in children and explore the possible dose adjustments required to reach the same plasma concentration as non-obese paediatrics. The difference in predicted maximum concentration (Cmax) and area under the curve (AUC) were significant between children with and without obesity across the age group 2 to 18 years old when a fixed-dose regimen was used. On the contrary, a weight-based dose regimen showed no difference in Cmax between obese and non-obese from 2 to 9 years old. Thus, when a fixed-dose regimen is to be administered, a 1.25- to 1.5-fold increase in dose is required in obese children to achieve the same Cmax concentration as non-obese children, specifically for children aged 5 years and above.
摘要:
儿童肥胖症的发病率在世界范围内持续上升,并导致一系列疾病,包括心血管疾病。儿童肥胖已被证明会影响各种化合物的血浆浓度,包括氨氯地平.尽管如此,关于肥胖对氨氯地平药代动力学的影响以及需要调整剂量的信息以前尚未研究过.这项研究应用了基于生理的药代动力学模型,并建立了一个儿科肥胖人群,以评估肥胖对儿童氨氯地平药代动力学的影响,并探索达到与非肥胖儿科相同的血浆浓度所需的可能剂量调整。当使用固定剂量方案时,在2至18岁年龄段的肥胖儿童和非肥胖儿童之间,预测的最大浓度(Cmax)和曲线下面积(AUC)的差异显着。相反,基于体重的给药方案显示,2~9岁肥胖与非肥胖人群的Cmax无差异.因此,当固定剂量方案被施用时,肥胖儿童需要增加1.25至1.5倍的剂量才能达到与非肥胖儿童相同的Cmax浓度,特别适用于5岁及以上的儿童。