Details

Autor(en) / Beteiligte

• Ferreira, Joaquim J.
• Poewe, Werner
• Rascol, Olivier
• Stocchi, Fabrizio
• Antonini, Angelo
• Moreira, Joana
• Guimarães, Bruno
• Rocha, José‐Francisco
• Soares‐da‐Silva, Patrício

Titel

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

Ist Teil von

• Movement disorders, 2022-11, Vol.37 (11), p.2272-2283

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• ABSTRACT Background Inhibiting catechol‐O‐methyltransferase extends the plasma half‐life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) experiencing motor fluctuations. Objectives To evaluate the effects of once‐daily opicapone on levodopa plasma pharmacokinetics and motor response when added to two different levodopa dosing regimens. Methods A total of 24 patients with PD and motor fluctuations were enrolled in an exploratory, open‐label, modified cross‐over trial. Participants first received levodopa/carbidopa 500/125 mg (five intakes) for 2 weeks and were then randomly assigned (1:1) to levodopa/carbidopa 400/100 mg given over either four or five daily intakes plus opicapone 50 mg for an additional 2 weeks. Levodopa 12‐hour pharmacokinetics was the primary outcome (ie, excluding the effect of last/evening levodopa/carbidopa intake), with motor complications evaluated as secondary outcomes. Results Over 12‐hour pharmacokinetics and compared with five‐intake levodopa/carbidopa 500/125 mg without opicapone, maximal levodopa concentrations were similar or nonsignificantly higher on both levodopa/carbidopa 400/100 mg regimens plus opicapone. Despite a 100 mg lower total levodopa/carbidopa daily dose, adding opicapone 50 mg at least doubled the levodopa plasma half‐life and minimal concentrations, with a significant ≈30% increase in total exposure. The levodopa fluctuation index was only significantly lower for the five intakes plus opicapone regimen (difference of −71.8%; P < 0.0001). Modifications to levodopa pharmacokinetics were associated with decreased off time and increased on time. Conclusions Combining opicapone 50 mg with a 100 mg lower daily dose of levodopa provides higher levodopa bioavailability with avoidance of trough levels. Despite the lower levodopa dose, modifying the levodopa pharmacokinetic profile with opicapone was associated with decreased off time and increased on time. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society Adjustments of levodopa dose size and/or frequency are common approaches to manage response fluctuations. However, the addition of opicapone in lower levodopa doses resulted in significant increases in levodopa exposure, leading to improved clinical outcomes. This will allow physicians to individually adjust the levodopa regimen that best suits patients' needs.