TOXICITY OF ANTI-AIDS AGENTS ON THE BONE MARROW

抗艾滋病药物对骨髓的毒性

基本信息

批准号：
2028439
负责人：
JEAN-PIERRE C SOMMADOSSI
金额：
$ 25.54万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-01-01 至 1998-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2028439
关键词：
antiAIDS agent bone marrow cytochrome P450 cytotoxicity drug adverse effect drug interactions enzyme inhibitors enzyme mechanism gene expression liver cells nucleoside analog purine /pyrimidine metabolism tissue /cell culture uridine monophosphate zidovudine

项目摘要

The objective of this program is to continue and expand ongoing studies on the mechanism by which pyrimidine nucleoside analog active against HIV such as 3'azido-3'-deoxythymidine and congeners exert toxicity on bone marrow and other cells. The elicitation of these mechanisms may permit the development of a combination therapy with modulating agents that protect or reverse host toxicity without impairment of the anti-HIV activity of the drug under scrutiny. This project has two major aims: 1) the description of the biochemical and molecular mechanism responsible for the effects of AZT and its metabolite, 3'-amino-3'-deoxythymidine (AMT) in human marrow cells; and 2) the detailed characterization of the enzymatic reduction of AZT to AMT in human hepatocytes with the evaluation of potential drug-drug interactions through the cytochrome P- 450 pathway.

该计划的目标是继续并扩大正在进行的研究嘧啶核苷类似物抗HIV作用机制的研究例如 3'azido-3'-deoxythymidine 及其同类物对骨产生毒性骨髓和其他细胞。这些机制的引发可能允许开发具有调节剂的联合疗法保护或逆转宿主毒性而不损害抗艾滋病病毒正在审查药物的活性。该项目有两个主要目标： 1) 负责的生化和分子机制的描述用于 AZT 及其代谢物 3'-氨基-3'-脱氧胸苷的作用 (AMT) 存在于人骨髓细胞中； 2）详细表征人肝细胞中 AZT 酶促还原为 AMT 通过细胞色素 P- 评估潜在的药物相互作用 450 途径。

项目成果

期刊论文数量（31）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antiretroviral activity, biochemistry, and pharmacokinetics of 3'-azido-2',3'-dideoxy-5-methylcytidine.

3-azido-2,3-dideoxy-5-methylcytidine 的抗逆转录病毒活性、生物化学和药代动力学。

DOI：
10.1111/j.1749-6632.1990.tb17858.x
发表时间：
1990
期刊：
Annals of the New York Academy of Sciences
影响因子：
5.2
作者：
Schinazi,RF;Chu,CK;Eriksson,BF;Sommadossi,JP;Doshi,KJ;Boudinot,FD;Oswald,B;McClure,HM
通讯作者：
McClure,HM

Cellular pharmacology of 3'-azido-3'-deoxythymidine with evidence of incorporation into DNA of human bone marrow cells.

3-叠氮基-3-脱氧胸苷的细胞药理学以及掺入人骨髓细胞 DNA 的证据。