title: Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers.
abstract: OBJECTIVE
  Absorption, biotransformation and elimination of safinamide, an enantiomeric α-aminoamide derivative developed as an add-on therapy for Parkinson's disease patients, were studied in healthy volunteers administered a single oral dose of 400 mg (14)C safinamide methanesulphonate, labelled in metabolically stable positions.
  
  
  METHODS
  Pharmacokinetics of the parent compound were investigated up to 96 h, of (14)C radioactivity up to 192/200 h post-dose.
  
  
  CONCLUSIONS
  Maximum concentration was achieved at 1 h (plasma, median Tmax) for parent drug and at 7 and 1.5 h for plasma and whole blood (14)C radioactivity, respectively. Terminal half-lives were about 22 h for unchanged safinamide and 80 h for radioactivity. Safinamide deaminated acid and the N-dealkylated acid were identified as major metabolites in urine and plasma. In urine, the β-glucuronide of the N-dealkylated acid and the monohydroxy safinamide were also characterized. In addition, the glycine conjugate of the N-dealkylated acid and 2-[4-hydroxybenzylamino]propanamide were tentatively identified as minor urinary metabolites.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Chiara
authors.initials: C
authors.lastname: Leuratti
authors.forename: Marco
authors.initials: M
authors.lastname: Sardina
authors.forename: Paolo
authors.initials: P
authors.lastname: Ventura
authors.forename: Alessandro
authors.initials: A
authors.lastname: Assandri
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
mesh_terms: D000328:Adult; D000409:Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D001596:Benzylamines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy; D055815:Young Adult
chemical_list: D001596:Benzylamines; C092797:safinamide; D000409:Alanine