Levodopa and 3-OMD levels in Parkinson patients treated with Duodopa

Abstract

We studied 19 patients (14 men, 5 women, Hoehn and Yahr (H&Y) ≥ 3) with advanced Parkinson's disease (PD) attending the Parkinson Institute, Milan, whose motor fluctuations and dyskinesia were not controlled by oral medications. After all oral PD medications had been withdrawn, they received a duodenal levodopa infusions (Duodopa, Solvay Pharmaceuticals) for 14 h/day through a transabdominal port; levodopa boluses were administered in the morning and during “off” periods. The patients were evaluated by means of the UPDRS in the morning (“off”) and 60–120 min after the infusion (“on”) at baseline and for a mean follow-up of 13.5 ± 12.5 months (up to 36 months in 10 patients:). Levodopa ( l-DOPA) and its metabolites were determined by HPLC with electrochemical detection. l-DOPA concentrations tended to higher in the afternoon (2008 ± 345 vs 1713 ± 274 ng/mL) and correlated with the daily dose. O-methyldopa (OMD) levels correlated with l-DOPA levels, and the OMD/ l-DOPA ratios were stable over the day. There was a relationship between decreasing UPDRS III scores and decreasing OMD/ l-DOPA ratios. Dyskinesia (UPDRS IV, items 32–34) showed a clear improvement over time but there was no clear relationship with l-DOPA and OMD levels, or the OMD/ l-DOPA ratio. The l-DOPA/dose ratio was stable over time, whereas OMD levels and the OMD/ l-DOPA ratio decreased. It is conceivable that continuous infusion decreases metabolism possibly due to a reduction in methyl donor availability, as demonstrated by the increase in total homocysteine levels. Our results do not support the development of tolerance even after several months of continuous infusion, and indicate that pharmacodynamic factors play a role in afternoon off periods.