PMID: 10934669: Variable absorption of carbidopa affects levodopa metabolism

[janet paterson <janet313@xxxxxxxxxxx>]

Variable absorption of carbidopa affects both peripheral and central
levodopa metabolism.

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).

8 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.


J Clin Pharmacol 2000 Aug;40(8):854-60
Durso R, Evans JE, Josephs E, Szabo G, Evans B, Fernandez HH, Browne TR
Department of Neurology, Boston Veterans Administration Medical Center,
Massachusetts, USA.
PMID: 10934669


janet paterson
53 now / 44 dx cd / 43 onset cd / 41 dx pd / 37 onset pd
tel: 613 256 8340 url: ";
email: janet313@xxxxxxxxxxx smail: POBox 171 Almonte Ontario K0A 1A0 Canada