Veng-Pedersen P
Biopharm Drug Dispos. 1987 Mar-Apr;8(2):185-203. doi: 10.1002/bdd.2510080209.
Most commonly drug absorption is evaluated with a reference dosing given on separate occasions. The assumption that no change in drug disposition is taking place between the drug administrations is often violated resulting in errors in the calculations. A novel deconvolution method is presented which exactly compensates for a change in drug clearance. The method is based on a model independent disposition decomposition-recomposition technique. The distribution function is obtained from an i.v. administration by disposition decomposition. This distribution function is assembled together with the elimination kinetics containing the perturbed clearance to construct the perturbed disposition function in the subsequent disposition recomposition operation. The perturbed absorption response is finally deconvolved using the corresponding perturbed disposition function. It is shown that the perturbed clearance can be obtained from the log-linear terminal disposition phase once the distribution function has been obtained from an i.v. administration. The proposed method is implemented in an algorithm and computer program DCONB and demonstrated using human cimetidine drug level data from an i.v. and oral administration. The usage of DCONB is identical to DECONV previously published. It requires only regular sums of exponentials to be fitted to drug level data. Such fittings are routinely done in pharmacokinetics thereby enabling DCONB to be implemented very simply.
最常见的情况是，药物吸收通过在不同时间给予的参考剂量来评估。在药物给药之间药物处置没有变化的假设常常被违反，从而导致计算错误。本文提出了一种新的去卷积方法，该方法能精确补偿药物清除率的变化。该方法基于一种与模型无关的处置分解 - 重组技术。分布函数通过处置分解从静脉注射给药中获得。这个分布函数与包含受干扰清除率的消除动力学一起组装，以在随后的处置重组操作中构建受干扰的处置函数。最终使用相应的受干扰处置函数对受干扰的吸收响应进行去卷积。结果表明，一旦从静脉注射给药中获得了分布函数，就可以从对数线性末端处置阶段获得受干扰的清除率。所提出的方法在算法和计算机程序DCONB中实现，并使用来自静脉注射和口服给药的人西咪替丁药物水平数据进行了验证。DCONB的使用方法与之前发表的DECONV相同。它只需要将指数的常规和拟合到药物水平数据上。这种拟合在药代动力学中是常规操作，因此使得DCONB能够非常简单地实现。
