A regression analytical model of serum levodopa metabolic profile in Parkinson's disease
Year: 2026
Type: article
Abstract: No methods to assess efficacy of levodopa-associated therapy by blood sampling in Parkinson’s disease (PD) have been established. In this study, we investigated levodopa associated metabolites to characterize their associations with medication and clinical symptoms in PD patients. Comprehensive metabolome analysis using plasma from PD and controls was performed in two independent cohorts (PD: 109, controls: 32; PD: 145, controls: 45). In another validation cohort [251 PD patients (16 de novo, 17 receiving only dopamine-receptor agonists, 218 receiving levodopa/benserazide or levodopa/carbidopa with/without other parkinsonian drugs) and 40 age-matched controls], serum levels of levodopa and its six metabolites were examined by liquid chromatography-mass spectrometry. The association of each metabolite with clinical parameters, medication, and enzymic genotypes was investigated. Significant increases in 3-methoxytyrosine and homovanillic acid were observed in PD patients administered levodopa/benserazide or levodopa/carbidopa. Serum levels of levodopa and five of its metabolites were significantly increased in PD patients administered levodopa and were related to the levodopa or entacapone dose but not to disease severity. Levodopa levels were more effectively preserved in PD patients given levodopa/benserazide than in those given levodopa/carbidopa, especially when taken with entacapone. Each dopamine or 3-methoxytyramine level was efficiently expressed with a numerical model using levodopa, entacapone, and selegiline doses as variables, indicative of its application for drug efficacy monitoring. Benserazide (25 mg) blocked AADC and preserved levodopa levels more effectively than carbidopa (10 mg), and entacapone provided a concomitant effect on levodopa level preservation. The drug efficacy of levodopa-associated medication could be monitored by dopamine or 3-methoxytyramine levels.
Source: Heliyon
Authors: Akiko Chukyo, Motoki Fujimaki, Naoko Kaga, Hikari Taka, Yuanzhe Li, Shin-Ichi Ueno, Haruka Takeshige-Amano, Manabu Funayama, Tomohiro Ishimaru, Kengo Miyamoto, Hirofumi Teranishi, Taku Hatano, Kei-Ichi Ishikawa, Yutaka Oji, Akio Mori, Taiji Tsunemi, Yuta Ishiguro, Kensuke Daida, Yoko Imamichi, Yukiko Sasazawa, Tetsushi Kataura, Mitsuhiro Kitagawa, Noriko Nishikawa, Masaya Imoto, Takashi Ueno, Osamu Komori, Yoshiki Miura, Wado Akamatsu, Nobutaka Hattori, Shinji Saiki
Institutions: Juntendo University, Seikei University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,270
Awards: Development of anti-PD drugs based on neuronal autophagy activation system, Identification of Parkinson's disease progression markers based on skeletal muscle-brain axis, Research on PD pathogenesis based on polyamine metabolism using multiomics analysis, Interrogating the autophagy-metabolism-cell death axis in iPSC-based Parkinson's disease models, Identification of Parkinson disease-specific mitochondrial pathogenesis for disease-modifying therapy, Elucidation of the mechanisms of the Parkinson's disease genes and Lewy Body formation and alpha-synuclein propagation mechanisms
OpenAlex ID: W7130399137