CORTICOSTEROID PHARMACOKINETICS & PHARMACODYNAMICS

我们目前的工作包括开发一种药物动力学 新近批准的反向药物地拉韦定(DLV)的模型 转录酶抑制剂，用于联合疗法治疗艾滋病。 在开发过程中，该药物在几次试验中使用 “低谷”血浆浓度的自适应反馈控制。一个 典型的起始方案是876.1(摩尔(400毫克)，口服，每隔 8小时。亲本DLV(也称为U90)和代谢物(N-DLV或 U96)浓度作为反馈。动力学模型具有 给药进入吸收部位，然后一级吸收(Ka) 在一段滞后的时间之后。DLV分布于中枢和外周 平衡率由C1d(C1d=Vc(Kcp))控制的舱室 =VP(KPC)。DLV从中央隔室通过以下方式消除 并联容限(饱和)和一阶间隙 路径(CL90)。我们用Km和Km对可饱和路径进行参数化 固有间隙(CLI=Vmax/公里)。DLV，由 饱和途径被代谢成N-DLV，我们将其建模为 将药物分配到单个隔室中，药物通过 第一订单流程(CL96)。这一型号目前正被用于 分析40名患者的数据，作为2期临床试验的一部分 HIV感染者中的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.