Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, United Kingdom; The Walton Centre NHS Foundation Trust, Liverpool, L9 7LJ, United Kingdom.
School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, United Kingdom.
Int J Pharm. 2017 Feb 25;518(1-2):155-166. doi: 10.1016/j.ijpharm.2016.12.032. Epub 2016 Dec 28.
This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug.
本研究旨在确定是否有证据支持为获得所需剂量而操纵药物，这是儿科临床实践中的常见特征。使用系统评价数据来源，包括 PubMed、EMBASE、CINAHL、IPA 和 Cochrane 系统评价数据库。纳入考虑操纵任何剂型药物的剂量准确性、安全性或危害证据、生物利用度、患者体验、耐受性、污染以及操纵方法比较的研究。排除病例报告和信件。有 50 项研究符合纳入标准，其中 49 项涉及片剂的切割、分割、粉碎或分散。另一项研究涉及一种药物栓剂的操纵。未发现涉及口服胶囊或液体、直肠灌肠剂、雾化溶液、注射剂或透皮贴剂操纵的合格研究。24 项片剂研究使用重量和/或药物含量来考虑剂量准确性。在考虑使用改编药典规格的重量的研究中，符合这些规格的半片比例范围为 30%至 100%。18 项研究调查了操纵后的生物利用度、药代动力学或临床结果，其中包括 9 种延迟释放或控释制剂。在这 9 项研究中的每一项中，都给予了整个剂型的药物。只有一项研究是为了获得剂型的一部分并给予该部分而操纵药物。考虑患者感知的五项研究发现，必须操纵片剂不会对依从性产生负面影响。在这 49 项研究中，只有两项研究报告了对儿童进行的研究。本综述仅提供了有限的证据支持为儿童操纵药物。结果不能从剂型、操纵方法或同一药物的不同品牌之间进行推断。
