Bobillot Marianne, Delannoy Violaine, Trouillard Alexandre, Kinowski Jean Marie, Sanchez-Ballester Noelia Maria, Soulairol Ian
Department of Pharmacy, Nîmes University Hospital, 30900 Nîmes, France.
ICGM, Montpellier University, CNRS, ENSCM, 34090 Montpellier, France.
Pharmaceutics. 2024 Jan 17;16(1):119. doi: 10.3390/pharmaceutics16010119.
The pediatric population exhibits an important age-dependent heterogeneity in pharmacokinetics and pharmacodynamics parameters, resulting in differences in drug efficacy and toxicity compared to the adult population, particularly for neonates. Toxicity and efficacy divergences have been studied for active molecules, but the impact on the pharmacological parameters of excipients remains less well known. To fill this lack of knowledge, several initiatives have been started to gather information on the specific toxicity of excipients, such as the KIDS list or the STEP database. In order to contribute to this much-needed action, in this work, a compilation of the 219 formulations of oral liquid forms prescribed in pediatrics and neonatology units was established based on the summary of product characteristics. Then, for excipients found in more than 10% of the analyzed formulations, a review of their toxicity data was carried out using the STEP database. Finally, for a selection of 10 frequently used liquid forms, the amounts of excipients administered daily were calculated based on the recommended posology in the Summary of Product Characteristics (SPC) and compared with the recommended daily limits proposed by the European Medicine Agency. Pediatrics-adapted formulations are still rare, and it is not always possible to find safe alternatives to drugs containing excipients of interest.
儿科人群在药代动力学和药效学参数方面表现出重要的年龄依赖性异质性，这导致与成人相比，药物疗效和毒性存在差异，尤其是对于新生儿。已经对活性分子的毒性和疗效差异进行了研究，但辅料对药理学参数的影响仍鲜为人知。为了填补这一知识空白，已经启动了多项举措来收集辅料特定毒性的信息，例如KIDS清单或STEP数据库。为了为这一急需的行动做出贡献，在本研究中，根据产品特性摘要编制了儿科和新生儿科开具的219种口服液体制剂。然后，对于在超过10%的分析制剂中发现的辅料，使用STEP数据库对其毒性数据进行了综述。最后，对于选择的10种常用液体制剂，根据产品特性摘要（SPC）中推荐的剂量计算每日服用的辅料量，并与欧洲药品管理局提出的每日推荐限量进行比较。适合儿科的制剂仍然很少见，而且并非总是能够找到含有相关辅料的药物的安全替代品。
