title: Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson's disease.
abstract: Elevation of plasma total homocysteine concentrations were observed in levodopa/dopa decarboxylase inhibitor (DDI)-treated patients with Parkinson's disease (PD). Degradation of levodopa to 3-O-methyldopa via the enzyme catechol-O-methyltransferase (COMT) is a methyl group demanding reaction. It generates homocysteine from the methyl group donor methionine. But there are inconsistent outcomes, as most investigators determined homocysteine after an overnight washout of levodopa. They did not consider the acute effects of levodopa/DDI intake in relation with COMT inhibition on homocysteine bioavailability. The purpose of this study is to measure levels of homocysteine, levodopa, and its metabolite 3-O-methyldopa in plasma after reiterated oral levodopa/DDI administration with and without the COMT-inhibitor entacapone (EN). Sixteen PD patients received 100 mg levodopa/carbidopa three times on day 1 and with EN on day 2 under standardized conditions. Homocysteine concentrations increased on day 1 and generally over the whole interval. No significant ascent of homocysteine appeared on day 2 only. Levodopa bioavailability was higher on day 2 due to the COMT inhibition. No change of 3-O-methyldopa appeared between both days. The correlation coefficients between homocysteine, levodopa, and 3-O-methyldopa were higher on day 1 than on day 2. Rise of homocysteine does not only depend on the oral levodopa dose, but also on the acute intake of levodopa/DDI with or without COMT inhibition. Measurements of homocysteine should consider acute repeated levodopa/DDI applications, as homocysteine and metabolically related 3-O-methyldopa accumulate due to their long plasma half-life in contrast to short-living levodopa.
authors.affiliation: Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, Germany. th.mueller@alexius.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Dirk
authors.initials: D
authors.lastname: Woitalla
authors.forename: Siegfried
authors.initials: S
authors.lastname: Muhlack
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001682:Biological Availability; D002230:Carbidopa / Q000627:therapeutic use; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy; D014443:Tyrosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004338:Drug Combinations; D009570:Nitriles; C009265:carbidopa, levodopa drug combination; D006710:Homocysteine; D014443:Tyrosine; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa; C008404:3-methoxytyrosine