Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA.
Regul Toxicol Pharmacol. 2012 Jul;63(2):333-43. doi: 10.1016/j.yrtph.2012.04.002. Epub 2012 Apr 13.
TK Modeler 1.0 is a Microsoft® Excel®-based pharmacokinetic (PK) modeling program created to aid in the design of toxicokinetic (TK) studies. TK Modeler 1.0 predicts the diurnal blood/plasma concentrations of a test material after single, multiple bolus or dietary dosing using known PK information. Fluctuations in blood/plasma concentrations based on test material kinetics are calculated using one- or two-compartment PK model equations and the principle of superposition. This information can be utilized for the determination of appropriate dosing regimens based on reaching a specific desired C(max), maintaining steady-state blood/plasma concentrations, or other exposure target. This program can also aid in the selection of sampling times for accurate calculation of AUC(24h) (diurnal area under the blood concentration time curve) using sparse-sampling methodologies (one, two or three samples). This paper describes the construction, use and validation of TK Modeler. TK Modeler accurately predicted blood/plasma concentrations of test materials and provided optimal sampling times for the calculation of AUC(24h) with improved accuracy using sparse-sampling methods. TK Modeler is therefore a validated, unique and simple modeling program that can aid in the design of toxicokinetic studies.
TK Modeler 1.0 是一个基于 Microsoft Excel 的药代动力学（PK）建模程序，旨在帮助设计毒代动力学（TK）研究。TK Modeler 1.0 使用已知的 PK 信息预测单次、多次推注或饮食给药后测试物质的昼夜血液/血浆浓度。基于测试物质动力学的血液/血浆浓度波动使用单或双室 PK 模型方程和叠加原理进行计算。此信息可用于确定适当的给药方案，以达到特定的预期 C(max)、维持稳态血液/血浆浓度或其他暴露目标。该程序还可以帮助选择采样时间，以使用稀疏采样方法（一个、两个或三个样本）准确计算 AUC(24h)（昼夜血液浓度时间曲线下面积）。本文描述了 TK Modeler 的构建、使用和验证。TK Modeler 准确预测了测试物质的血液/血浆浓度，并提供了最佳的采样时间，使用稀疏采样方法可提高 AUC(24h)计算的准确性。因此，TK Modeler 是一个经过验证的、独特的、简单的建模程序，可以帮助设计毒代动力学研究。
