ACUTE EFFECTS OF COMT INHIBITION ON L-DOPA PHARMACOKINETICS IN PATIENTS TREATED WITH CARBIDOPA AND SELEGILINE

Citation
Tl. Davis et al., ACUTE EFFECTS OF COMT INHIBITION ON L-DOPA PHARMACOKINETICS IN PATIENTS TREATED WITH CARBIDOPA AND SELEGILINE, Clinical neuropharmacology, 18(4), 1995, pp. 333-337
Citations number
22
Categorie Soggetti
Pharmacology & Pharmacy",Neurosciences
Journal title
ISSN journal
03625664
Volume
18
Issue
4
Year of publication
1995
Pages
333 - 337
Database
ISI
SICI code
0362-5664(1995)18:4<333:AEOCIO>2.0.ZU;2-D
Abstract
The effects of acute catechol-O-methyltransferase (COMT) inhibition on L-DOPA pharmacokinetics were studied in 10 parkinsonian subjects on s table doses of L-DOPA/carbidopa and selegiline. Tolcapone, a reversibl e COMT inhibitor, was administered in four single ascending doses (50- 800 mg) randomly paired with placebo. Serial plasma concentrations of L-DOPA and its metabolites were measured, and patient diaries and clin ical ratings of dyskinesia were completed every 30 min for 6 h. Tolcap one increased the area under the curve of the plasma L-DOPA concentrat ion versus time curve and decreased the accumulation of homovanillic a cid. COMT inhibition increased ''on'' time and the duration of dyskine sia without affecting the maximal amplitude of dyskinesia. Tolcapone m ay be a useful adjunct to L-DOPA/carbidopa.