Variable absorption of carbidopa affects both peripheral and central levodopa metabolism

Carbidopa (CD) a competitive inhibitor of aromatic I-amino acid decarboxyla se that does not cross the blood-brain barrier, is routinely administered w ith levodopa (CD) to patients with Parkinson disease (PD) to reduce the per ipheral decarboxylation of LD to dopamine. Using a stable isotope-labeled f orm of LD, the authors examined in 9 PD patients the effects of variable CD absorption on peripheral and central LD metabolism. Subjects were administ ered orally 50 mg of CD followed in I hour by a slow bolus intravenous infu sion of 150 mg stable isotope-labeled LD (ring 1',2',3',4:5',6'-C-13). Eigh t patients underwent a lumbar puncture 6 hours following the infusion. Bloo d and cerebrospinal fluid (CSF) samples were analyzed for labeled and unlab eled metabolites using a combination of high-performance liquid chromatogra phy and mass spectrometry. When patients were divided into "slow" and "rapi d" CD absorption groups, significantly greater peripheral LD decarboxylatio n (as measured by area under the curve [AUC]-labeled serum HVA) was noted i n the poor absorbers (p = 0.05, Mann-Whitney U test). Elimination half-live s for serum LD did not differ between groups, suggesting a further capacity for decarboxylation inhibition in the "rapid" absorbers, A significant cor relation between A UC 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 absor bers had significantly more percent-labeled CSF HVA (60 vs. 49, p = 0.02, M ann-Whitney U test), indicating greater central-labeled DA production in th e better CD absorbers. The data suggest that peripheral aromatic I-amino ac id decarboxylase activity is not saturated at CD doses used in current prac tice. The authors believe that future studies to better examine a dose depe ndence of CD on peripheral LD decarboxylation and LD brain uptake are warra nted. (C) 2000 the American College of Clinical Pharmacology.