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Abstract

Amantadine is one of the most commonly used drugs for the control of tremor in Parkinson's disease. Additionally, it has an antiviral action in the prevention of type A influenza. It has been previously reported that amantadine is nearly completely eliminated in the urine. No metabolites have been detected. Surprisingly, in a case of amantadine overdose, several metabolites could be identified by gas chromatography/mass spectrometry. This finding prompted us to re-investigate the metabolism of amantadine under a therapeutic dosing regimen. The bulk of the dose was eliminated unchanged. However, eight metabolites could be identified. Besides N-acetylation which is the major metabolic pathway, several rather unusual metabolic pathways were observed: N-methylation, formation of Schiff bases and N-formiates. No metabolites with a hydroxylated adamantane ring system could be detected.