Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system
Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system
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DOI：
10.1111/bcp.13650
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发表时间：
2018-10-01
影响因子：
3.4
通讯作者：
Bermejo, Marival
中科院分区：
文献类型：
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作者：
del Moral Sanchez, Jose Manuel;Gonzalez-Alvarez, Isabel;Bermejo, Marival
目的 缺乏适当、有效和安全的制剂是儿科治疗中的常见问题。吞咽能力、感官偏好和剂量要求等关键因素决定了优化配方的必要性。临时生物制药分类系统（BCS）可作为风险分析和优化工具用于儿科制剂设计。本研究的目的是按照适用于三个儿科亚群（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。 方法阿苯达唑、苯并硝唑、伊维菌素、硝呋莫司、吡喹酮和氯胍选自世界卫生组织第五版儿童基本药物标准清单。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并且儿童患者和成人之间的被动膜渗透性没有变化。根据适合每个年龄阶段的不同剂量和体积，估计每种药物的 pBCS 类别，并与成人分类进行比较。结果所有六种药物在三个儿科亚群中均被归类为临时 pBCS。三种药物保持与成人相同的分类，伊维菌素和苯并硝唑在新生儿中的溶解度等级从低到高，氯胍在所有年龄阶段的溶解度从低到高。结论这六种药物的临时 pBCS 分类显示，与成人相比，儿科口服吸收的限制因素根据年龄阶段存在潜在变化。这些有价值的信息将有助于优化儿科剂量和制剂，并可以在比较不同制剂和儿科人群时识别生物等效性风险。
AimsUnavailability 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).MethodsAlbendazole, 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 logP comparison versus metoprolol logP 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.ResultsAll 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.ConclusionProvisional 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.