Monitoring of Blood L-DOPA and L-DOPA Metabolite Concentrations and Adverse Events in Patients with Advanced Parkinson's Disease Receiving L-DOPA and MAO Inhibitor Selegiline ((-)Deprenyl) Combination Therapy: A Clinical Study

摘要

As L-DOPA replacement is the main treatment for patients with Parkinson's disease, monitoring of the blood dopamine (DA) concentration is useful for prediction of peripheral adverse effects. We measured the blood concentration of L-DOPA and its metabolites in patients with advanced Parkinson's disease who were receiving L-DOPA and the monoamine oxidase type B (MAO-B) inhibitor, selegiline, and studied the relationship between adverse events and the blood concentrations of L-DOPA and its metabolites. The study subjects were patients with advanced Parkinson's disease for whom L-DOPA and selegiline had been prescribed since 2007 at Sakura Hospital, Toho University Medical Center. Blood sampling was carried out at 0,1,2 and 3 hours after L-DOPA administration. The blood concentrations of L-DOPA, DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-O-methyldopa (3-OMD) were measured using a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. We used hospital medical records to establish the age of the patients, and their gender, Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, L-DOPA dosing regime, use of selegiline in combination with L-DOPA, and adverse effects. Based on the information in the medical record, we investigated and classified patients into two groups according to whether or not they had suffered adverse events. There were no significant differences in age, disease history, Hoehn & Yahr severity, L-DOPA dosage or selegiline dosage per day between the groups. Significant inter-group differences were observed in UPDRS part I， which includes an item for hallucination, and UPDRS part IV, which includes an item for complications. No significant inter-group differences were observed for other itemis. The blood DA concentration (4.22+-2.67 ng/mL, n=24) in the group that had suffered adverse events one hour after administration of L-DOPA and selegiline was significantly higher than that (2.66+-2.08 ng/mL, n=19) in the group that had not (P=0.043). There were no significant inter-group differences in the blood concentrations of L-DOPA, DOPAC, and 3-OMD at any time. It is suggested that monitoring of L-DOPA and its metabolites in blood can be useful for indicating peripheral adverse effects of L-DOPA therapy in patients with advanced Parkinson's disease.