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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这是一项探索性观察性试验，用于调查青春期抗逆转录病毒药物动力学的变化。 众所周知，与成年人相比，对于许多抗逆转录病毒药物的口服血浆清除率高达200％。 但是，随着儿童成熟，与药物代谢变化相关的时间和因素尚未得到很好的定义。 这项研究将招募约60名受艾滋病毒感染的儿童，青少年和年轻人7-24岁，他们正在接受抗逆转录病毒药物。 所有受试者将在进入时进行一项密集的药代动力学研究，以准确定义其口服清除率（CL/F）。 在研究中，将继续使用贝叶斯药代动力学方法来确定用稀疏采样确定的CL/F年度纵向评估的一部分（约15-20）。 在青春期的不同临床阶段，将比较受试者之间CL/F的差异。 将评估的共同变化将是身体表面积，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。 这项研究的目的是收集描述性和初步数据，该数据将在未来的该人群中设计为重点和确定的药代动力学研究。