In vivo Quantitative ADME Studies

The % dose (or fraction metabolized) for each metabolite is calculated by summing the % dose calculated for each excretion pathway (urine or feces) of the metabolite and any subsequent secondary metabolites. The % dose for each excretion pathway is calculated by multiplying the percent abundance of a characterized metabolite on a radiometric chromatogram by the total radioactivity present in the evaluated sample (once extraction and column efficiencies have been taken into account). More detailed analysis would be required to calculate the fraction metabolized if secondary metabolites were formed from more than one primary metabolite (Bu et al., 2005, 2006). 

The systemic exposure of circulating metabolite is calculated by estimating the area under the curve for a mean radioactivity versus time plot (Fig. 15.7). The fraction of the systemic exposure contributed by a particular metabolite is calculated by dividing the AUC estimated for a particular metabolite by the AUC of the total radioactivity. Alternatively, the metabolite concentration time profile and metabolite concentrations can be constructed using nonradiometric bioanalytical techniques if metabolite standards are available. 

Example plasma radioactivity—time profile for radiolabeled ADME 

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