Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers

Pharmacology. 2013;92(3-4):207-16. doi: 10.1159/000354805. Epub 2013 Oct 11.


Background/aims: 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.

Results/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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / analogs & derivatives*
  • Alanine / blood
  • Alanine / pharmacokinetics
  • Alanine / urine
  • Benzylamines / blood
  • Benzylamines / pharmacokinetics*
  • Benzylamines / urine
  • Feces / chemistry
  • Healthy Volunteers
  • Humans
  • Male
  • Parkinson Disease / drug therapy
  • Young Adult


  • Benzylamines
  • safinamide
  • Alanine