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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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，与成人相比，幼儿的口服血浆清除率相差高达200%。 然而，随着儿童的成熟，药物代谢变化的时间和相关因素尚未得到很好的定义。 本研究将入组约60名正在接受抗逆转录病毒药物治疗的7-24岁HIV感染儿童、青少年和年轻人。 所有受试者将在入组时接受密集的药代动力学研究，以准确定义其口服清除率（CL/F）。 一个受试者子集（约15-20例）将继续参与研究，每年两次使用贝叶斯药代动力学方法对稀疏采样确定的CL/F进行纵向评价。 将比较处于青春期不同临床阶段的受试者之间的CL/F差异。 将评估的协变量为体表面积、肝脏体积、血清药物结合蛋白浓度和性激素。 此外，本研究将评价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。 本研究的目的是收集描述性和初步数据，以便将来在该人群中设计重点明确的药代动力学研究。