Tresperimus (Cellimis), a new immunosuppressive agent is mainly eliminated through an extensive nonhepatic metabolism, in which the oxidative deamination of the primary amine of the drug takes a preponderant part. We have previously demonstrated the ability of human plasma semicarbazide-sensitive amine oxidase (SSAO) to catalyze this reaction. Therefore, the suitability of human umbilical artery, a tissue combining a high SSAO activity with monoamine oxidase activity, to study tresperimus metabolism was tested, and the kinetic behavior of tissue-bound SSAO was compared with that of plasma soluble SSAO. All the oxidized metabolites resulting from the deamination of tresperimus and of two other metabolites, desaminopropyl derivatives of tresperimus and guanidinohexylamine, were formed in vascular homogenates. Chemical inhibition experiments demonstrated the major involvement of SSAO in the metabolism of these three compounds at physiologically relevant concentrations. The microsomal fraction was used to characterize tresperimus deamination. Tissue-bound and soluble SSAO exhibited similar K(m) values for the drug and K(I) values of tresperimus toward benzylamine metabolism, a classical SSAO substrate. The kinetic behavior of both enzymes seemed to argue in favor of a same catalytic entity. Human umbilical artery constituted a relevant in vitro model to demonstrate the predominant role of SSAO in tresperimus metabolism. Our results suggest that the possible role of SSAO as Phase I oxidative enzymes has to be considered in metabolism studies for drugs encompassing primary amine.