PHARMACOKINETICS OF LOPINAVIR CRUSHED VERSUS WHOLE TABLETS

洛匹那韦粉碎片与整片的药代动力学

• 批准号: 7951133
• 负责人: NATELLA Y RAKHMANINA
• 金额: $ 0.96万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951133
• 关键词: Alcohols; Caregivers; Childhood; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Deglutition; Development; Dose; Drug Kinetics; Ethanol toxicity; Exposure to; Film; Food; Funding; Grant; Institution; Lopinavir; Lopinavir/Ritonavir; Manufacturer Name; Mastication; Oral; Overdose; Patients; Population; Provider; Recommendation; Refrigeration; Research; Research Personnel; Resources; Solutions; Source; Tablets; Taste Perception; Techniques; Time; Treatment Failure; United States National Institutes of Health; Yogurt; high risk; liquid formulation; tablet formulation; viral resistance

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lopinavir/ritonavir is available as an oral solution for pediatric dosing. This liquid formulation has an unpleasant taste, contains 42% alcohol (with the potential to cause significant alcohol toxicity in accidental overdose), must be taken with food, is bulky and requires refrigeration, all of which are barriers to use in pediatric populations. A new film-coated tablet formulation has recently been approved in the U.S. that does not require refrigeration and may be taken without regard to meals. The prescribing information states that these tablets may not be crushed, broken or chewed, and the manufacturer does not plan to examine the pharmacokinetics of crushed tablets at this time. However, patients and caregivers are dosing pediatric patients with crushed tablets to overcome some of the limitations of the oral solution. If crushed tablet administration yields significantly lower systemic exposure to lopinavir than whole tablets, then patients using this administration technique will be at higher risk for development of viral resistance and treatment failure. This administration technique must be studied so that providers have evidence to support recommendations about this dose administration strategy. This study is aimed to describe the pharmacokinetics of lopinavir in pediatric patients after taking the whole tablet formulation and compare within the same subject to the pharmacokinetics after crushing the tablet formulation and mixing with pudding or yogurt. It is hypothesized that Lopinavir exposure in pediatric patients will be lower after taking a dose of the tablet formulation, crushed and mixed with pudding or yogurt, as compared to the exposure after taking a dose with tablets swallowed whole.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 洛匹那韦/利托那韦可作为儿童剂量的口服溶液。 这种液体制剂味道难闻，含有 42% 的酒精（意外过量服用可能会导致严重的酒精中毒），必须与食物一起服用，体积大且需要冷藏，所有这些都是儿科人群使用的障碍。 一种新的薄膜包衣片剂配方最近在美国获得批准，不需要冷藏，并且可以不考虑进餐情况服用。 处方信息指出，这些药片不得压碎、打碎或咀嚼，制造商目前不打算检查压碎药片的药代动力学。 然而，患者和护理人员正在给儿科患者服用粉碎药片，以克服口服溶液的一些局限性。 如果粉碎片剂给药产生的洛匹那韦全身暴露量显着低于整片片剂，那么使用这种给药技术的患者将面临更高的病毒耐药性和治疗失败的风险。 必须研究这种给药技术，以便提供者有证据支持有关这种剂量给药策略的建议。 本研究旨在描述儿童患者服用整个片剂后洛匹那韦的药代动力学，并在同一受试者中与粉碎片剂并与布丁或酸奶混合后的药代动力学进行比较。 据推测，与服用整片片剂后的暴露量相比，服用一定剂量的片剂、压碎并与布丁或酸奶混合后，洛匹那韦在儿科患者中的暴露量会较低。