Usefulness of Monitoring Blood L-dopa and L-dopa Metabolite Concentrations in Patients with Advanced Parkinson's Disease Receiving COMT Inhibitor Entacapone Combination Therapy

摘要

For patients with advanced Parkinson's disease (PD) it is important to maintain stable efficacy of anti-Parkinsonian drugs such as L-dopa. To study the usefulness of monitoring the blood concentrations of L-dopa and L-dopa metabolites, we examined the efficacy of L-dopa and catechol-O-methyltransferase (COMT) inhibitor combination therapy and measured the blood concentrations of L-dopa and L-dopa metabolites. The study subjects were patients with advanced PD for whom entacapone (Comtan) had been prescribed at Sakura Hospital, Toho University Medical Center. We focused on 12 patients who had been taking100 mg of L-dopa 3 times per day, with additionally prescribed entacapone. Blood sampling was carried out at 0,1,2 and 3 hours after L-dopa administration. The blood concentrations of L-dopa, dopamine (DA)3 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-O-methyldopa (3-OMD) were measured using a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system and compared before and after combined administration of entacapone with L-dopa. Although the maximum blood concentration (C_(max))of L-dopa at1hour after L-dopa administration showed no change after entacapone combination with L-dopa compared with that before administration, the blood concentration of L-dopa at 2 and 3 hours after combined treatment tended to be higher than that after administration of L-dopa alone. The area under the curve from 0 to 3 hours (AUC)0-3 of L-dopa and DA showed no change between before and after combined administration of entacapone. The AUC0.3 of 3-OMD after entacapone combination with L-dopa was significantly lower than that after L-dopa alone. On the other hand, the AUC0.3 of DOPAC after entacapone in combination with L-dopa was significantly higher than that after L-dopa alone. The score for part III of the Unified Parkinson's Disease Rating Scale (UPDRS) was 21.4±2.7 for L-dopa alone and 20.9±2.8 for entacapone combined with L-dopa, although the improvement was not significant. Although the blood DA concentration was not significantly increased by entacapone in combination with L-dopa, nausea occurred in one patient due to an increase of the blood DA concentration after administration of entacapone in combination with L-dopa, As entacapone dia not yield any dramatic improvement of symptoms in patients with advanced PD, multiple evaluation is required in order to judge the efficacy of this drug. It is suggested that monitoring of L-dopa and L-dopa metabolites in blood can provide a usefiil indicator of the efficacy of L-dopa therapy in patients with advanced PD.