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Are high doses of carbidopa a concern? A randomized, clinical trial in Parkinson's disease
Author(s) -
Brod Lissa S.,
Aldred Jason L.,
Nutt John G.
Publication year - 2012
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.24998
Subject(s) - carbidopa , dose , medicine , aromatic l amino acid decarboxylase , pharmacokinetics , levodopa , chemotherapy , anesthesia , pharmacology , parkinson's disease , dopamine , disease
Recommended doses of carbidopa are 75‐200 mg/day. Higher doses could inhibit brain aromatic amino‐acid decarboxylase and reduce clinical effects. We compared 4‐week outpatient treatments with carbidopa (75 and 450 mg/day) administered with L ‐dopa on the subjects' normal schedule. After each treatment phase, subjects had two 2‐hour L ‐dopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding 4 weeks, and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and L ‐dopa and carbidopa plasma concentrations were monitored during the infusions. Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high‐carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four L ‐dopa infusions, although AUC for plasma L ‐dopa was modestly increased with 450 mg of carbidopa. Nine subjects reported that the high‐carbidopa outpatient phase was associated with greater response to L ‐dopa. Doses of 450 mg/day of carbidopa did not reduce the responses to L ‐dopa infusion, extending the safe range of carbidopa to 450 mg/day. © 2012 Movement Disorder Society