Noriyuki Miyaue1, Yuko Hosokawa2, Akira Yoshida2, Yuki Yamanishi2, Satoshi Tada2, Rina Ando2, Hayato Yabe3, Masahiro Nagai2. 1. Department of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Tohon, Ehime, Japan; Department of Neurology, Saiseikai Matsuyama Hospital, Matsuyama, Ehime, Japan. Electronic address: miyaue@m.ehime-u.ac.jp. 2. Department of Clinical Pharmacology and Therapeutics, Ehime University Graduate School of Medicine, Tohon, Ehime, Japan. 3. Department of Neurology, Saiseikai Matsuyama Hospital, Matsuyama, Ehime, Japan.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Silvia Rota; Daniele Urso; Daniel J van Wamelen; Valentina Leta; Iro Boura; Per Odin; Alberto J Espay; Peter Jenner; K Ray Chaudhuri Journal: Transl Neurodegener Date: 2022-10-13 Impact factor: 9.883