Document Detail


Variable absorption of carbidopa affects both peripheral and central levodopa metabolism.
MedLine Citation:
PMID:  10934669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Carbidopa (CD), a competitive inhibitor of aromatic l-amino acid decarboxylase that does not cross the blood-brain barrier, is routinely administered with levodopa (LD) to patients with Parkinson disease (PD) to reduce the peripheral decarboxylation of LD to dopamine. Using a stable isotope-labeled form of LD, the authors examined in 9 PD patients the effects of variable CD absorption on peripheral and central LD metabolism. Subjects were administered orally 50 mg of CD followed in 1 hour by a slow bolus intravenous infusion of 150 mg stable isotope-labeled LD (ring 1',2',3',4',5',6'-13C). Eight patients underwent a lumbar puncture 6 hours following the infusion. Blood and cerebrospinal fluid (CSF) samples were analyzed for labeled and unlabeled metabolites using a combination of high-performance liquid chromatography and mass spectrometry. When patients were divided into "slow" and "rapid" CD absorption groups, significantly greater peripheral LD decarboxylation (as measured by area under the curve [AUC]-labeled serum HVA) was noted in the poor absorbers (p = 0.05, Mann-Whitney U test). Elimination half-lives for serum LD did not differ between groups, suggesting a further capacity for decarboxylation inhibition in the "rapid" absorbers. A significant correlation between AUC serum CD and percent-labeled HVA in CSF was found for all patients (R = 0.786, p = 0.02). "Rapid" as compared to "slow" CD absorbers had significantly more percent-labeled CSF HVA (60 vs. 49, p = 0.02, Mann-Whitney U test), indicating greater central-labeled DA production in the better CD absorbers. The data suggest that peripheral aromatic l-amino acid decarboxylase activity is not saturated at CD doses used in current practice. The authors believe that future studies to better examine a dose dependence of CD on peripheral LD decarboxylation and LD brain uptake are warranted.
Authors:
R Durso; J E Evans; E Josephs; G Szabo; B Evans; H H Fernandez; T R Browne
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  40     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-11-30     Completed Date:  2000-11-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  854-60     Citation Subset:  IM    
Affiliation:
Department of Neurology, Boston Veterans Administration Medical Center, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Absorption
Adult
Aged
Antiparkinson Agents / pharmacokinetics*
Brain / metabolism*
Carbidopa / pharmacokinetics*
Child
Homovanillic Acid / pharmacokinetics
Humans
Levodopa / pharmacokinetics*
Middle Aged
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Levodopa; 306-08-1/Homovanillic Acid; 38821-49-7/Carbidopa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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