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.
BACKGROUND/AIMS: Absorption, biotransformation and elimination of safinamide, an enantiomeric α-aminoamide derivative developed as an add-on therapy for Parkinson's diseasepatients, 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. Safinamidedeaminated 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.