Marquez-Megias Silvia, Ramon-Lopez Amelia, Más-Serrano Patricio, Diaz-Gonzalez Marcos, Candela-Boix Maria Remedios, Nalda-Molina Ricardo
School of Pharmacy, Miguel Hernández University, 03550 San Juan de Alicante, Spain.
Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), 03010 Alicante, Spain.
Pharmaceutics. 2021 Aug 12;13(8):1244. doi: 10.3390/pharmaceutics13081244.
Adalimumab is a monoclonal antibody used for inflammatory bowel disease. Due to its considerably variable pharmacokinetics, the loss of response and the development of anti-antibodies, it is highly recommended to use a model-informed precision dosing approach. The aim of this study is to evaluate the predictive performance of different population-pharmacokinetic models of adalimumab for inflammatory bowel disease to determine the pharmacokinetic model(s) that best suit our population to use in the clinical routine. A retrospective observational study with 134 patients was conducted at the General University Hospital of Alicante between 2014 and 2019. Model adequacy of each model was evaluated by the distribution of the individual pharmacokinetic parameters and the NPDE plots whereas predictive performance was assessed by calculating bias and precision. Moreover, stochastic simulations were performed to optimize the maintenance doses in the clinical protocols, to reach the target of 8 mg/L in at least 75% of the population. Two population-pharmacokinetic models were selected out of the six found in the literature which performed better in terms of adequacy and predictive performance. The stochastic simulations suggested the benefits of increasing the maintenance dose in protocol to reach the 8 mg/L target.
阿达木单抗是一种用于治疗炎症性肠病的单克隆抗体。由于其药代动力学差异很大，会出现反应丧失和抗抗体产生的情况，因此强烈建议采用模型指导的精准给药方法。本研究的目的是评估不同的阿达木单抗群体药代动力学模型对炎症性肠病的预测性能，以确定最适合我们群体用于临床常规的药代动力学模型。2014年至2019年期间，在阿利坎特综合大学医院对134名患者进行了一项回顾性观察研究。通过个体药代动力学参数的分布和NPDE图评估每个模型的模型适用性，而通过计算偏差和精密度来评估预测性能。此外，进行了随机模拟，以优化临床方案中的维持剂量，使至少75%的人群达到8 mg/L的目标。从文献中找到的六个模型中选出了两个人群体药代动力学模型，它们在适用性和预测性能方面表现更好。随机模拟表明了在方案中增加维持剂量以达到8 mg/L目标的益处。
