Assessment of complex peptide degradation pathways via structured multicompartmental modeling approaches: the metabolism of dynorphin A1-13 and related fragments in human plasma.

摘要: Peptide metabolic pathways in blood or other tissues are often complex because multiple enzyme systems involved the degradation of parent drug and its metabolites. Michaelis-Menten-type studies with isolated enzymes have been frequently employed for evaluating metabolism peptides. Alternatively, selective inhibitors evaluation area under drug- metabolite-time profiles employed. We tested this study usefulness a multicompartmental pharmacokinetic approach assessment apparent first-order dynorphin A1-13 up to fourth metabolite generation human plasma. This kinetic analysis proved instrumental clarifying ambiguous not easily detectable by methods (enzyme inhibition noncompartmental analysis) lack specific specificity problems analytical technique The proposed fitting was also highly suitable verify overall suggested testing whether rate constants obtained these describe profile after Dyn degradation. Local sensitivity DYNA 1-13 revealed that model was, however, able adequately identify on own all parameters A1-13. Thus, method beneficial correctness methods.