Fasting state is one of the factors associated with plasma levodopa fluctuations during levodopa‒carbidopa intestinal gel treatment

• Published in: Parkinsonism & related disorders Vol. 91; pp. 55 - 58
• Main Authors: Miyaue, Noriyuki, Hosokawa, Yuko, Yoshida, Akira, Yamanishi, Yuki, Tada, Satoshi, Ando, Rina, Yabe, Hayato, Nagai, Masahiro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2021
• Subjects: Aged; Antiparkinson Agents - blood; Antiparkinson Agents - pharmacokinetics; Carbidopa - pharmacokinetics; Drug Combinations; Eating - drug effects; Fasting - blood; Fasting state; Female; Gels; Humans; Intestines - drug effects; Levodopa - blood; Levodopa - pharmacokinetics; levodopa‒carbidopa intestinal gel; Lunch - drug effects; Male; Migrating motor complex; Motor Activity - drug effects; Parkinson Disease - blood; Parkinson Disease - drug therapy; Parkinson's disease; Migrating motor complex; Parkinson's disease; Levodopa pharmacokinetics; levodopa‒carbidopa intestinal gel; Fasting state
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2021.09.001

Some patients with Parkinson's disease (PD) undergoing levodopa‒carbidopa intestinal gel (LCIG) treatment experience motor fluctuations in the afternoon. The migrating motor complex, a specific periodic migrating contraction pattern occurring in the stomach and small intestine during the fasting state, can affect drug absorption. We aimed to compare the pharmacokinetic parameters between two conditions (with and without lunch) and assessed the influence of the fasting state on the levodopa pharmacokinetics in LCIG treatment. We evaluated the levodopa pharmacokinetics from 12:00 p.m. to 6:00 p.m. in 10 LCIG-treated PD patients in the presence and absence of lunch. The maintenance dose of LCIG correlated strongly with the mean plasma concentration of levodopa in the absence (r = 0.94, coefficient of determination (R2) = 0.89, p < 0.001) or presence of lunch (r = 0.96, R2 = 0.93, p < 0.001). Comparison of the pharmacokinetic parameters revealed that the coefficient of variation was significantly greater in the condition without lunch than in the condition with lunch (p = 0.004): 16.73% (4.88%) without lunch and 9.22% (3.80%) with lunch. There were no significant differences in the mean plasma concentration of levodopa (p = 0.49) and area under the plasma concentration‒time curve (p = 0.27) between the two conditions. Plasma concentrations of levodopa fluctuated more in patients undergoing LCIG treatment without than with lunch. Our results indicate that a small amount of food intake may be a better corrective approach for worsening of symptoms in the fasting state rather than additional levodopa. •LCIG-treated PD patients can experience motor fluctuations in the afternoon.•We compared levodopa pharmacokinetics in conditions without and with lunch.•Plasma concentrations of levodopa fluctuated more after LCIG without lunch.•A fasting state may cause fluctuating plasma concentrations of levodopa due to MMC.•A small amount of food intake may be effective in worsening symptoms during fasting.