Objective: We analyzed diurnal variation of levodopa plasma concentration in large number of patients with Parkinson’s disease (PD) to clarify the pattern of diurnal variation.

Background: Levodopa is still the most effective agent for the treatment for PD. However, levodopa has pharmacokinetic disadvantages including its relatively short plasma elimination half-life and variable absorption from the gastrointestinal tract. Therefore intra- and inter-individual variability in the pharmacokinetics of levodopa is observed in PD patients. It is important to clarify feature of the variability for rational pharmacological treatment.

Methods: We have measured levodopa plasma concentration of PD patients in clinical practice. Data of levodopa concentrations in PD patients who had taken a levodopa/carbidopa (100/10mg) tablet, three times a day after meals were selected for this study. The data of levodopa concentrations at every two hours from morning until evening were available.

Results: A total of 102 PD patients (50 males and 52 females) were eligible. The mean age, disease duration, and the Hoehn and Yahr scale were 72.9 years, 5.9 years, and 2.8, respectively. The mean of maximum levodopa concentration (Cmax) was 7.4μM. The mean of Cmax in female subjects was 8.2μM, which was significantly higher than that in male subjects (6.6μM). Cmax varied among different individuals, and the inter-individual variability of the Cmax showed 8.2-fold difference. Cmax had no significant correlation with age, disease duration, and the Hoehn and Yahr scale. The mean levodopa concentration at each clock time was 0.46μM (8am), 3.12μM (10am), 3.29μM (12pm), 5.18μM (2pm), 3.96μM (4pm), 2.48μM (6pm), 4.84μM (8pm), and 3.41μM (10pm). When levodopa concentration at four hours after taking levodopa was higher than that at two hours after taking levodopa, we defined it as “delayed on” phenomenon. The “delayed on” was not observed in 36 subjects. However, 20 subjects showed the “delayed on” only in the morning. Six subjects showed it only in the afternoon. Four subjects showed it only in the evening. 35 subjects showed it twice a day. Two subjects showed it after every meal.

Conclusions: There was 8.2-fold difference in the Cmax of levodopa among individuals. The “delayed on” phenomenon in the morning was observed in approximately half of the PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diurnal-variation-of-levodopa-plasma-concentration-in-patients-with-parkinsons-disease/