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
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.