Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO).

Tresperimus (Cellimis), a new immunosuppressive agent, is mainly eliminated in the rat through metabolism, in which the oxidative deamination of the primary amine of the drug plays a major role. We have previously demonstrated in vivo the significant involvement of semicarbazide-sensitive amine oxidase (SSAO) in this reaction. Rat aorta, a tissue with one of the highest specific SSAO activities, was tested as a new in vitro model to elucidate tresperimus metabolism, using a combination of liquid chromatography/mass spectrometry (LC/MS) and high-performance liquid chromatography (HPLC) analyses.

In vitro metabolism of tresperimus by human vascular semicarbazide-sensitive amine oxidase.

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.

Involvement of semicarbazide-sensitive amine oxidase in tresperimus metabolism in human and in rat.

The metabolism of tresperimus, a new immunosuppressive agent, was investigated in vivo and in vitro in rat and in human. Two metabolic pathways were identified at each side of the molecule with two deamination reactions on the spermidine moiety and hydrolysis of the amide bond leading to the liberation of guanidinohexylamine. As the major metabolic pathway of the drug seemed to be the oxidative deamination, the capacity of different amine oxidases to metabolize tresperimus was then tested using in vivo experiments in rat and in vitro studies in rat and human plasma.