Gasthuys Elke, Sandra Louis, Statelova Marina, Vertzoni Maria, Vermeulen An
Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 157 84 Athens, Greece.
Pharmaceuticals (Basel). 2023 Dec 28;17(1):53. doi: 10.3390/ph17010053.
To date, food-drug interactions in the pediatric population remain understudied. The current food effect studies are mostly performed in adults and do not mimic the real-life situation in the pediatric population. Since the potential benefits of food effect studies performed in pediatrics should be counterbalanced with the burden that these studies pose to the patients, alternative research strategies should be evaluated. The present study aimed to evaluate whether population pharmacokinetics (popPK) using data in beagle dogs and human adults could reliably assess food effects relevant for the pediatric population. PopPK was utilized to understand the performance of paracetamol under different dosing conditions (when the participants were fasted, with a reference meal, and with infant formula) in human adults ( = 8) and beagle dogs ( = 6) by constructing models to derive the pharmacokinetic parameters and to evaluate the food effects in both species. A two-compartment model with a single input function for the absorption phase best described the profiles of paracetamol in the beagle dogs. In the human adults, a one-compartment model with a dual input function for the absorption phase best described the data. The simulated profiles for the different dosing conditions demonstrated that both the human adults' and beagle dogs' simulations were able to acceptably describe the plasma concentration-time profiles of paracetamol observed in a representative pediatric population, which opens up perspectives on pediatric-relevant food effect predictions. However, the obtained results should be carefully interpreted, since an accurate validation of these findings was not possible due to the scarcity of the literature on observed pediatric data.
迄今为止，儿科人群中的食物 - 药物相互作用仍未得到充分研究。当前的食物效应研究大多在成年人中进行，并未模拟儿科人群的现实生活情况。由于在儿科进行食物效应研究的潜在益处应与这些研究给患者带来的负担相权衡，因此应评估替代研究策略。本研究旨在评估使用比格犬和成年人类数据的群体药代动力学（popPK）能否可靠地评估与儿科人群相关的食物效应。通过构建模型以推导药代动力学参数并评估两个物种的食物效应，利用群体药代动力学来了解对乙酰氨基酚在成年人类（n = 8）和比格犬（n = 6）不同给药条件下（参与者禁食时、食用参考餐时以及食用婴儿配方奶粉时）的表现。具有吸收相单一输入函数的二室模型最能描述比格犬体内对乙酰氨基酚的情况。在成年人类中，具有吸收相双输入函数的一室模型最能描述数据。不同给药条件下的模拟曲线表明，成年人类和比格犬的模拟都能够可接受地描述在代表性儿科人群中观察到的对乙酰氨基酚血浆浓度 - 时间曲线，这为与儿科相关的食物效应预测开辟了前景。然而，由于关于儿科观察数据的文献稀缺，无法对这些结果进行准确验证，因此所得结果应谨慎解读。
