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Central levodopa metabolism in Parkinson's disease after administration of stable isotope—labeled levodopa
Author(s) -
Durso Raymon,
Evans James E.,
Josephs Ephraim,
Szabo George K.,
Evans Barbara A.,
Handler Joseph S.,
Jennings Dana,
Browne Thomas R.
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410420305
Subject(s) - levodopa , homovanillic acid , cerebrospinal fluid , carbidopa , bolus (digestion) , lumbar puncture , parkinson's disease , medicine , in vivo , endocrinology , metabolism , chemistry , gastroenterology , serotonin , biology , disease , receptor , microbiology and biotechnology
Abstract We report the use of a new stable isotope–labeled form of levodopa (LD) to examine in vivo central LD metabolism in Parkinson's disease (PD). Eight patients representing a wide spectrum of disease severity were administered 50 mg of carbidopa orally followed in 1 hour by an intravenous bolus of 150 mg of stable isotope–labeled LD ( ring ‐1′,2′,3′,4′,5′,6′‐ 13 C6). Serial blood samples were taken every 30 to 60 minutes and a lumbar puncture was performed 6 hours after the infusion. The average percentage of labeled homovanillic acid (HVA) in lumbar cerebrospinal fluid (CSF) was 54% (SD, 9%; range, 34–67%). The mean CSF labeled HVA concentration was 34.7 ng/ml (SD, 20.2 ng/ml; range, 11.3–67.9 ng/ml). Area under the curve for labeled serum LD closely predicted CSF labeled HVA concentrations ( r = 0.747, p = 0.033). Labeled CSF HVA levels did not significantly correlate with either quality or duration of response to the labeled LD dose. In a similar manner, labeled CSF HVA concentrations were not influenced by duration of disease or previous daily LD dosage. These findings support the hypothesis that levodopa‐induced benefit in PD is not severely limited by a defect in central levodopa metabolism.