title: Are high doses of carbidopa a concern? A randomized, clinical trial in Parkinson's disease.
abstract: 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.
authors.affiliation: Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center, Portland, Oregon, USA.
authors.forename: Lissa S
authors.initials: LS
authors.lastname: Brod
authors.forename: Jason L
authors.initials: JL
authors.lastname: Aldred
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D002230:Carbidopa / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D002230:Carbidopa