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Detection of tolcapone in the cerebrospinal fluid of parkinsonian subjects.
Russ, H; Müller, T; Woitalla, D; Rahbar, A; Hahn, J; Kuhn, W.
Naunyn Schmiedebergs Arch Pharmacol ; 360(6): 719-20, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10619191

ABSTRACT

The cerebral availability of the peripherally and centrally acting catechol-O-methyltransferase (COMT) inhibitor tolcapone is not known in humans. Therefore, we determined the concentration of tolcapone in cerebrospinal fluid (CSF) of 12 parkinsonian subjects 1-4 h after oral application of 200 mg of the drug. The mean concentration was 56.4+/-35.5 nmol/l (mean +/- SD). This concentration was calculated to cause 75.2+/-15% (mean +/- SD) inhibition of COMT in CSF. Thus, tolcapone efficiently inhibits COMT after crossing the blood-brain barrier in humans.


Subject(s)
Antiparkinson Agents/cerebrospinal fluid , Benzophenones/cerebrospinal fluid , Enzyme Inhibitors/cerebrospinal fluid , Parkinson Disease/cerebrospinal fluid , Parkinson Disease/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Benzophenones/administration & dosage , Benzophenones/adverse effects , Blood-Brain Barrier , Catechol O-Methyltransferase/cerebrospinal fluid , Catechol O-Methyltransferase Inhibitors , Chromatography, High Pressure Liquid , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Female , Humans , Male , Middle Aged , Nitrophenols , Tolcapone
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