DEMONS—A NEW DECONVOLUTION METHOD FOR ESTIMATING DRUG ABSORBED AT DIFFERENT TIME INTERVALS AND/OR DRUG DISPOSITION MODEL PARAMETERS USING A MONOTONIC CUBIC SPLINE
✍ Scribed by ZHILING YU; STEPHEN S. HWANG; SUNEEL K. GUPTA
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 198 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
DeMonS Ð a new numerical deconvolution method for estimating the amount of drug absorbed at dierent time intervals and/or drug disposition model parameters Ð is presented here. In DeMonS, the amount of drug absorbed at dierent time intervals and/or drug disposition model parameters are the unknown parameters to be calculated. The Fritsch±Butland non-decreasing cubic spline was constructed from the cumulative amount of drug absorbed±time data directly derived from the calculated amount of drug absorbed at dierent time intervals. The drug absorption rate, which is the derivative of this non-decreasing cubic spline, is therefore represented by a piecewise non-negative quadratic function. The drug concentrations were obtained by convoluting the drug absorption rate quadratic function with the drug disposition model function.
The nonlinear optimization method with simple parameter bounds was used to estimate the optimal set of unknown parameters by minimizing the sum of squares of residuals between the observed and predicted drug concentrations. DeMonS has been applied to (i) the griseofulvin data for estimating drug absorbed at dierent time intervals when the drug disposition model parameters were determined separately from intravenous data, (ii) veralipride double-peak phenomenon data to estimate simultaneously the percentage of cumulative veralipride absorbed and the veralipride disposition model parameters without reference intravenous data, (iii) a comparative bioequivalence study of gastrointestinal therapeutic system (GITS) pseudoephedrine HCI (PeHCI) controlledrelease oral dosage forms when the drug disposition model parameters were not available, and (iv) estimation of both drug disposition model parameters and the absorption rate of drug from Testoderm 1 (testosterone transdermal system) in the presence of endogenous testosterone production. DeMonS was implemented using MATLAB 1 and NAG 1 MATLAB Toolbox, and is available for Windows 3.1. &1997