Zamir Ammara, Rasool Muhammad Fawad, Alqahtani Faleh, Alqhtani Hussain, Ahmad Tanveer
Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Pharmaceutics. 2024 Dec 4;16(12):1553. doi: 10.3390/pharmaceutics16121553.
Diphenhydramine is an anti-tussive used periodically to treat seasonal colds, contact dermatitis, and anaphylactic reactions. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of diphenhydramine in predicting its systemic exposure among healthy pediatrics (children and adolescents) by leveraging data files from adults (young and elderly).
The data profiles comprising serum/plasma concentration over time and parameters related to diphenhydramine were scrutinized via exhaustive literature analysis and consolidated in the PK-Sim software version 11.1. This modeling methodology commences with developing an adult model and then translating it to the pediatrics which compares the predicted concentration-time datasets with the reported values.
The accuracy of model anticipations was then assessed for each pharmacokinetics (PK) variable, i.e., the area under the curve from 0 to infinity (AUC), maximal serum/plasma concentration (C), and clearance of the diphenhydramine in plasma (CL) by employing the predicted/observed ratios (R), and average fold error (AFE), which fell within the pre-defined benchmark of 2-fold. The predicted and observed C values for pediatrics were 3-fold greater in comparison to the young adults following a 25 mg dose depicting a need to monitor dosage schedules among children closely.
These model-based anticipations confirmed the authenticity of the developed pediatric model and enhanced the comprehension of developmental variations on PK of diphenhydramine. This may assist healthcare professionals in ensuring the significance of lifespan applicability in personalized dose regimens, promoting therapeutic efficacy and minimizing side effects in chronic conditions among children.
苯海拉明是一种用于治疗季节性感冒、接触性皮炎和过敏反应的止咳药。本研究旨在通过利用来自成年人（年轻人和老年人）的数据文件，建立一个基于生理学的苯海拉明药代动力学（PBPK）模型，以预测其在健康儿科人群（儿童和青少年）中的全身暴露情况。
通过详尽的文献分析，仔细研究了包含血清/血浆浓度随时间变化以及与苯海拉明相关参数的数据概况，并将其整合到PK-Sim软件版本11.1中。这种建模方法首先建立一个成人模型，然后将其转化为儿科模型，将预测的浓度-时间数据集与报告值进行比较。
然后通过使用预测/观察比值（R）和平均倍数误差（AFE），对每个药代动力学（PK）变量，即从0到无穷大的曲线下面积（AUC）、最大血清/血浆浓度（C）和苯海拉明在血浆中的清除率（CL）进行模型预测准确性评估，这些值均落在预先定义的2倍基准范围内。在给予25mg剂量后，儿科人群的预测C值与年轻成年人相比高3倍，这表明需要密切监测儿童的用药剂量。
这些基于模型的预测证实了所建立的儿科模型的真实性，并增强了对苯海拉明药代动力学发育差异的理解。这可能有助于医疗保健专业人员确保在个性化给药方案中考虑寿命适用性的重要性，提高治疗效果，并最大限度地减少儿童慢性病中的副作用。
