Institute of Molecular and Cellular Biology of Miguel Hernandez University, Avda de la Universidad s/n, 03202, Elche (Alicante), Spain.
Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550, Alicante, Spain.
Br J Clin Pharmacol. 2018 Oct;84(10):2231-2241. doi: 10.1111/bcp.13650. Epub 2018 Jul 17.
Unavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need for optimization of formulations. The provisional Biopharmaceutics Classification System (BCS) can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical disease drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children).
Albendazole, benznidazole, ivermectin, nifurtimox, praziquantel and proguanil were selected from the 5th edition of the Model List of Essential Medicines for Children from the World Health Organization. Paediatric drug solubility classification was based on dose number calculation. Provisional permeability classification was based on log P comparison versus metoprolol log P value, assuming passive diffusion absorption mechanisms and no changes in passive membrane permeability between paediatric patients and adults. pBCS classes were estimated for each drug, according to different doses and volumes adapted for each age stage and were compared to the adult classification.
All six drugs were classified into provisional pBCS in the three paediatric subpopulations. Three drugs maintained the same classification as for adults, ivermectin and benznidazole changed solubility class from low to high in neonates and proguanil changed from low to high solubility in all age stages.
Provisional pBCS classification of these six drugs shows potential changes in the limiting factors in oral absorption in paediatrics, depending on age stage, compared to the adult population. This valuable information will aid the optimization of paediatric dosing and formulations and can identify bioinequivalence risks when comparing different formulations and paediatric populations.
在儿科治疗中，药物制剂无法获得或缺乏适当、有效且安全的制剂是常见问题。吞咽能力、感官偏好和剂量要求等关键因素决定了优化制剂的必要性。临时生物药剂学分类系统（BCS）可用于儿科制剂设计，作为风险分析和优化工具。本研究的目的是根据适应三个儿科亚人群（新生儿、婴儿和儿童）的临时儿科 BCS（pBCS）分类，对六种被忽视的热带病药物进行分类。
从世界卫生组织《儿童基本药物标准清单》第 5 版中选择阿苯达唑、苯硝唑、伊维菌素、硝呋替莫、吡喹酮和丙氧嘧啶。儿科药物溶解度分类基于剂量数计算。临时渗透性分类基于 logP 与美托洛尔 logP 值的比较，假设被动扩散吸收机制，以及儿科患者和成人之间被动膜通透性没有变化。根据不同年龄阶段适应的不同剂量和体积，估计每种药物的 pBCS 类别，并与成人分类进行比较。
在三个儿科亚人群中，这六种药物均被归类为临时 pBCS。三种药物的分类与成人相同，伊维菌素和苯硝唑在新生儿中的溶解度从低变为高，丙氧嘧啶在所有年龄阶段的溶解度从低变为高。
与成人相比，这些六种药物的临时 pBCS 分类显示了儿科口服吸收的限制因素在不同年龄阶段可能发生变化。这些有价值的信息将有助于优化儿科剂量和制剂，并在比较不同制剂和儿科人群时识别生物等效性风险。
