ANTIRETROVIRAL THERAPY PHARMACOKINETICS DURING PUBERTY

青春期抗逆转录病毒治疗药代动力学

• 批准号: 7605115
• 负责人: Elizabeth Jane McFarland
• 金额: $ 7.61万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605115
• 关键词: Adolescent; Adult; Age; Anti-Retroviral Agents; Binding Proteins; Body Surface Area; Child; Clinical; Computer Retrieval of Information on Scientific Projects Database; Data; Drug Kinetics; Enrollment; Evaluation; Fatty acid glycerol esters; Funding; Future; Goals; Gonadal Steroid Hormones; Grant; HIV; Institution; Liver; Mitochondria; Nucleosides; Oral; Personal Satisfaction; Pharmaceutical Preparations; Plasma; Population; Puberty; Research; Research Personnel; Resources; Reverse Transcriptase Inhibitors; Sampling; Serum; Source; Staging; Time Factors; Toxic effect; United States National Institutes of Health; antiretroviral therapy; design; drug metabolism; lipid metabolism; young adult

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. This is an exploratory, observational trial to investigate changes in antiretroviral medication pharmacokinetics during puberty. It is well know that for many antiretroviral drugs' oral plasma clearance differs by as much as 200% for young children compared to adults. However, the timing and factors associated with the change in drug metabolism as the child matures have not been well defined. This study will enroll approximately 60 HIV infected children, adolescents, and young adults, age 7-24 years, who are receiving antiretroviral medications. All subjects will undergo an intensive pharmacokinetic study at entry to accurately define their oral clearance (CL/F). A subset of the subjects (approximately 15-20) will continue in the study for twice yearly longitudinal evaluations of CL/F determined with sparse sampling, using a Bayesian pharmacokinetic approach. Differences in CL/F will be compared between subjects at different clinical stages of puberty. Co-variates that will be assessed will be body surface area, liver volume, serum drug binding protein concentrations, and sex hormones. In addition, the study will evaluate relationships between intracellular nucleoside reverse transcriptase inhibitor concentrations and mitochondrial toxicity, fat distribution, and lipid metabolism. The goal of this study is to collect descriptive and preliminary data that will enable the design of focused and definitive pharmacokinetic studies in this population in the future.

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 中心，不一定是研究者的机构。 这是一项探索性、观察性试验，旨在研究青春期抗逆转录病毒药物药代动力学的变化。 众所周知，对于许多抗逆转录病毒药物，幼儿的口服血浆清除率与成人相比相差高达 200%。 然而，随着儿童成熟，与药物代谢变化相关的时间和因素尚未明确。 这项研究将招募约 60 名感染艾滋病毒的儿童、青少年和年轻人，年龄在 7 至 24 岁之间，正在接受抗逆转录病毒药物治疗。 所有受试者在进入时都将接受深入的药代动力学研究，以准确定义其口服清除率 (CL/F)。 一部分受试者（大约 15-20 名）将继续参与该研究，使用贝叶斯药代动力学方法，对通过稀疏采样确定的 CL/F 进行每年两次的纵向评估。 将比较青春期不同临床阶段的受试者之间 CL/F 的差异。 将评估的协变量包括体表面积、肝脏体积、血清药物结合蛋白浓度和性激素。 此外，该研究还将评估细胞内核苷逆转录酶抑制剂浓度与线粒体毒性、脂肪分布和脂质代谢之间的关系。 本研究的目标是收集描述性和初步数据，以便将来能够设计针对该人群的集中且明确的药代动力学研究。