CORTICOSTEROID PHARMACOKINETICS & PHARMACODYNAMICS

我们目前的工作包括开发一种药代动力学 药物delavirdien（DLV）的模型，最近批准的逆转 转录酶抑制剂，用于治疗艾滋病的联合方案。 在开发过程中，在几次试验中， “谷”血浆浓度的自适应反馈控制。 一 典型的起始方案是876.1（摩尔（400毫克），口服，每 8小时 母体DLV（也称为U90）和代谢产物（N-DLV或 U96）浓度作为反馈进行测定。 动力学模型具有 团注输入到吸收部位，然后是一级吸收（ka） 在滞后时间之后。 DLV分布于中央和外周 平衡速率由Cld（Cld = Vc（kcp））控制的隔室 = Vp（kpc）。 DLV从中央室中消除，通过 并联容量限制（饱和）和一阶间隙 CL90）。 我们用Km来参数化可饱和路径， 固有清除率（CLi = Vmax/Km）。 DLV由 饱和途径代谢为N-DLV，我们将其建模为 分配到单个隔室中，药物从该隔室中被清除， 一阶过程（CL 96）。 该模型目前用于 分析来自40名患者的数据，作为2期临床试验的一部分， HIV感染者的DLV。

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.