CORTICOSTEROID PHARMACOKINETICS & PHARMACODYNAMICS

皮质类固醇药代动力学

• 批准号: 6480880
• 负责人: WILLIAM J. JUSKO
• 金额: $ 15.58万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6480880
• 关键词: AIDS; bacteria; bioengineering /biomedical engineering; biomedical resource; health care; immunology; infection; inflammation; lymphatic system; statistics /biometry; technology /technique; virus

Our current work has involved development of a pharmacokinetic model for the drug delavirdien (DLV), a recently-approved reverse transcriptase inhibitor, used in combination regimens to treat AIDS. During development, the drug was dosed, in several trials, using adaptive feedback control of 'trough' plasma concentrations. A typical starting regimen is 876.1 (moles (400 mg), given orally, every 8 hours. Both parent DLV (also called U90) and metabolite (N-DLV or U96) concentrations were assayed as feedback. The kinetic model has bolus inputs into an absorptive site, then first order absorption (ka) after a lag time. DLV distributes into central and peripheral compartments with rate of equilibration governed by Cld (Cld = Vc(kcp = Vp(kpc). DLV is eliminated, from the central compartment, by parallel capacity-limited (saturable) and first order clearance pathways (CL90). We parameterize the saturable pathway by Km and intrinsic clearance (CLi = Vmax/Km). DLV which is cleared by the saturable pathway is metabolized to N-DLV, which we modeled as distributing into a single compartment from which drug is cleared by a first order process (CL96). This model is currently being used to analyze data from 40 patients as part of a Phase 2 clinical trial of DLV in HIV infected patients.

我们目前的工作涉及开发药代动力学 Delavirdien药物的模型（DLV），这是一种最近批准的反向 转录酶抑制剂，用于治疗艾滋病的组合方案。 在开发过程中，在几次试验中对药物进行了剂量 “槽”等离子体浓度的自适应反馈控制。 一个 典型的起始方案为876.1（摩尔（400毫克），口服，每个 8小时。 父级DLV（也称为U90）和代谢物（N-DLV或 U96）浓度被分析为反馈。 动力学模型具有 推注输入吸收性位点，然后输入一阶吸收（KA） 滞后时间。 DLV分布到中央和外围 由CLD控制的平衡速率的车厢（CLD = VC（KCP） = VP（KPC）。 DLV从中央隔室消除 平行容量限制（饱和）和一阶清除率 途径（CL90）。 我们通过km和 内在间隙（CLI = VMAX/KM）。 DLV由 饱和途径被代谢为N-DLV，我们将其建模为 分发到一个单个隔间，从中用药物清除药物 一阶过程（CL96）。 该模型当前正在使用 分析来自40名患者的数据，作为第二阶段临床试验的一部分 HIV感染患者的DLV。