PACTG(PEDIATRIC AIDS CLINICAL TRIAL GROUP) 1058 : PHARMACOKINETIC STUDIES

PACTG（儿科艾滋病临床试验组）1058：药代动力学研究

• 批准号: 7603580
• 负责人: ANN J MELVIN
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603580
• 关键词: AIDS clinical trial group; Adult; Affect; Age; Anti-Retroviral Agents; Child; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytochromes; Data; Drug Combinations; Drug Kinetics; Funding; Grant; HIV Protease Inhibitors; Hepatic; Institution; Label; Licensing; Numbers; Pattern; Pharmaceutical Preparations; Protease Inhibitor; Research; Research Personnel; Resistance; Resources; Safety; Source; System; Testing; Treatment Protocols; United States National Institutes of Health; Viral Load result; antiretroviral therapy; base; experience; non-nucleoside reverse transcriptase inhibitors; pediatric AIDS

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. Antiretroviral therapy for HIV-infected children has become highly complex and individualized due to extensive antiretroviral treatment experience, the availability of 20 different antiretroviral drugs, and the ability to define complex resistance patterns by genotypic and phenotypic testing. Rather than using a small number of tested fixed drug combinations, clinicians are basing treatment decisions on factors such as palatability, tolerability, safety, convenience, and most prominently, resistance patterns. Cross-resistance between antiretrovirals leads to situations where it is not possible to construct a regimen likely to achieve and maintain an undetectable viral load without using combinations, often of 4 or more drugs, that have not been studied in children (and often not in adults). Because all of the available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and HIV protease inhibitors (PIs) are metabolized by and affect hepatic cytochrome systems (through induction, inhibition, or both mechanisms), combinations of two or more of these drugs produce complex pharmacokinetic interactions. In addition to the deficit of information on interacting drug combinations, many of the licensed antiretrovirals do not have FDA-approved labeling for children or for children below a certain age. This study proposes to investigate the pharmacokinetic (PK) interactions in children of several popular drug regimens for which no PK data is currently available.

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。 由于有广泛的抗逆转录病毒治疗经验，有20种不同的抗逆转录病毒药物可供使用，并有能力通过基因型和表型检测确定复杂的耐药模式，因此，对艾滋病毒感染儿童的抗逆转录病毒治疗已变得非常复杂和个性化。 临床医生不是使用少量经过测试的固定药物组合，而是根据适口性、耐受性、安全性、方便性以及最重要的耐药模式等因素做出治疗决定。 抗逆转录病毒药物之间的交叉耐药性导致不可能在不使用联合药物（通常是4种或更多种药物）的情况下构建一种可能实现和维持无法检测的病毒载量的方案，这些药物尚未在儿童中进行过研究（并且通常不是在成人中）。 由于所有可用的非核苷类逆转录酶抑制剂（NNRTI）和HIV蛋白酶抑制剂（PI）均由肝细胞色素系统代谢并影响肝细胞色素系统（通过诱导、抑制或两种机制），因此这些药物中的两种或更多种联合使用会产生复杂的药代动力学相互作用。 除了缺乏关于相互作用的药物组合的信息外，许多获得许可的抗逆转录病毒药物没有FDA批准的儿童或特定年龄以下儿童的标签。 本研究旨在研究目前尚无PK数据的几种常用药物方案在儿童中的药代动力学（PK）相互作用。