title: Central levodopa metabolism in Parkinson's disease after administration of stable isotope-labeled levodopa.
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.
authors.affiliation: Department of Neurology, Boston University School of Medicine and Boston Veterans Administration Medical Center, MA 02130, USA.
authors.forename: R
authors.initials: R
authors.lastname: Durso
authors.forename: J E
authors.initials: JE
authors.lastname: Evans
authors.forename: E
authors.initials: E
authors.lastname: Josephs
authors.forename: G K
authors.initials: GK
authors.lastname: Szabo
authors.forename: B A
authors.initials: BA
authors.lastname: Evans
authors.forename: J S
authors.initials: JS
authors.lastname: Handler
authors.forename: D
authors.initials: D
authors.lastname: Jennings
authors.forename: T R
authors.initials: TR
authors.lastname: Browne
mesh_terms: D000328:Adult; D000368:Aged; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D007980:Levodopa / Q000378:metabolism* / Q000627:therapeutic use*; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D007980:Levodopa; D006719:Homovanillic Acid