CORTICOSTEROID PHARMACOKINETICS & PHARMACODYNAMICS

皮质类固醇药代动力学

• 批准号: 6205820
• 负责人: WILLIAM J. JUSKO
• 金额: --
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205820
• 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药代动力学的开发 药物 delavirdien (DLV) 的模型，这是最近批准的逆向药物 转录酶抑制剂，用于联合治疗艾滋病。 在开发过程中，在多项试验中，该药物的剂量使用 “谷”血浆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，每次 8小时。 母体 DLV（也称为 U90）和代谢物（N-DLV 或 U96)浓度被测定作为反馈。 动力学模型有 推注输入吸收位点，然后一级吸收 (ka) 经过一段时间的滞后。 DLV分布为中枢和外周 室的平衡率受 Cld 控制 (Cld = Vc(kcp = Vp(kpc)。 DLV 被消除，从中央隔间，通过 并行容量限制（饱和）和一阶间隙 途径（CL90）。 我们用 Km 参数化可饱和路径， 固有间隙（CLi = Vmax/Km）。 DLV 由 可饱和途径代谢为 N-DLV，我们将其建模为 分配到一个隔室中，药物由一个隔室清除 第一订单流程 (CL96)。 该模型目前被用于 作为 2 期临床试验的一部分，分析 40 名患者的数据 HIV 感染患者的 DLV。