RT Journal Article SR Electronic T1 Involvement of Semicarbazide-Sensitive Amine Oxidase in Tresperimus Metabolism in Human and in Rat JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 735 OP 741 VO 29 IS 5 A1 Philippe Claud A1 Paul Padovani A1 Jean-Pierre Guichard A1 Yves Artur A1 Romuald Lainé YR 2001 UL http://dmd.aspetjournals.org/content/29/5/735.abstract AB 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. The increase of tresperimus plasma levels induced by the administration of hydralazine, an irreversible in vivo inhibitor of semicarbazide-sensitive amine oxidase (SSAO), reflected the major involvement of this enzyme in tresperimus metabolism. This result was confirmed in vitro in rat and human plasma by the use of semicarbazide, a specific SSAO inhibitor. As opposed to rat plasma, human plasma may be an interesting in vitro model to study the metabolism of a drug extensively metabolized by SSAO such as tresperimus. Indeed, SSAO activity was significantly higher in human plasma than in rat plasma. The second metabolic pathway of the drug, which only occurred in rat plasma, appeared thus as the major route of tresperimus metabolism in this biological matrix. The American Society for Pharmacology and Experimental Therapeutics