Pharmacokinetics of Opicapone and Effect on Comt and Levodopa Pharmacokinetics in Patients with Parkinson's Disease

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Conference Proceeding

Publication Date


Publication Title

J Mov Disord


Objective: To evaluate the pharmacokinetics and pharmacodynamics of opicapone in Parkinson's disease (PD). Background: Opicapone is a novel, peripherally-acting, highly-selective catechol-O-methyltransferase (COMT) inhibitor being developed in the U.S. for PD as an adjunct to levodopa-related motor fluctuations. Methods: Patients with stable PD were administered once-daily opicapone (50mg) in the evening on Days 1-14. Serial blood samples for determination of plasma opicapone concentrations and erythrocyte soluble COMT (S-COMT) activity were collected after the first and last opicapone dose. Participants were randomized to receive carbidopa/levodopa (25/100mg) every 3 or 4 hours (Q3H or Q4H) on pharmacokinetic sampling days, and their usual carbidopa/levodopa regimen on other days. Serial plasma samples for determination of levodopa and 3-O-methyldopa concentrations were collected after the first three levodopa doses on Day1 (prior to opicapone dosing), Day2 and Day15. The effect of opicapone on levodopa pharmacokinetics and S-COMT activity was assessed. Mean values (±standard errors) are presented. Results: The study enrolled 16 participants (men=10, women=6). Day 14 opicapone Cmax and AUC0-last were 459±63 ng/mL and 2022±196 ng∗hr/mL, respectively. At steady-state (Day14), COMT activity was inhibited on average by 76.3±1.4%, compared to baseline. After opicapone administration, total levodopa AUC (ng∗hr/mL) increased from Day1 (Q3H, 7339±949; Q4H, 7570±946) to Day15 (Q3H, 11714±1674; Q4H, 13159±1509). Peak-to-trough fluctuation in levodopa concentrations for the third daily levodopa dose were reduced from 88.3±15.2% and 173±18.3% for the Q3H and Q4H regimens on Day1 to 58.1±8.7% and 94.3±9.2%, respectively, on Day15. Trough levodopa concentrations for the third daily levodopa dose increased from 547±51 and 227±28 ng/mL for the Q3H and Q4H regimens on Day1 to 1142±201 and 749±125 ng/mL, respectively, on Day15. Conclusions: Once-daily opicapone 50mg resulted in substantial and prolonged COMT inhibition, which increased systemic exposure to levodopa and led to both decreased peak-to-trough fluctuations in levodopa concentrations and to higher trough levodopa concentrations.



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