A MULTIDIMENSIONAL DECONVOLUTION METHOD FOR EVALUATING THE ABSORPTIONOF DRUGS UNDERGOING REVERSIBLE METABOLISM AND PRESYSTEMIC METABOLITE FORMATION

A general multidimensional deconvolution method is developed primarily for application to the bioavailability assessment of drugs with rever sible metabolism. The proposed approach involves fitting continuous fu nctions to the experimental data and then applying a numerical deconvo lution algorithm to the fitted curves. It is shown how the method may be used to determine the rates and extends of drug absorption and pres ystemic formation of interconversion metabolites. The proposed method is implemented as a FORTRAN subroutine called DCVSYS for the general m ultidimensional deconvolution problem involving any continuous functio ns and as a user-friendly PC-compatible program called NDCREV for eval uating the absorption of drugs undergoing reversible metabolism. The m ethods and computer programs are demonstrated by application to simula ted drug and metabolite concentrations for a drug with reversible meta bolism.