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

Abstract

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.

• Authors: Chiara Leuratti, Marco Sardina, Paolo Ventura, Alessandro Assandri, Markus Müller, Martin Brunner
• Journal: Pharmacology (Pharmacology) Vol. 92 Issue 3-4 Pg. 207-16 ( 2013) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 24136086 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 S. Karger AG, Basel.

Chemical References

• Benzylamines
• safinamide
• Alanine

Topics

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