Burhanuddin Khairulanwar, Mohammed Afzal, Badhan Raj K S
School of Pharmacy, College of Health and Life Science, Aston University, Birmingham B4 7ET, UK.
Pharmaceutics. 2024 Apr 2;16(4):489. doi: 10.3390/pharmaceutics16040489.
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 (C) 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 C 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 C concentration as non-obese children, specifically for children aged 5 years and above.
全球范围内，儿童肥胖症的发病率持续上升，并引发了一系列疾病，包括心血管疾病。研究表明，儿童肥胖会影响多种化合物的血浆浓度，其中包括氨氯地平。然而，此前尚未对肥胖对氨氯地平药代动力学的影响以及剂量调整的必要性进行研究。本研究应用基于生理的药代动力学模型，建立了儿童肥胖人群模型，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童相同血浆浓度所需的可能剂量调整。当采用固定剂量方案时，2至18岁肥胖儿童与非肥胖儿童之间预测的最大浓度（C）和曲线下面积（AUC）差异显著。相反，基于体重的剂量方案显示，2至9岁肥胖儿童与非肥胖儿童的C值没有差异。因此，当采用固定剂量方案给药时，肥胖儿童需要将剂量增加1.25至1.5倍，才能达到与非肥胖儿童相同的C浓度，尤其是5岁及以上的儿童。
