Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson’s disease

ABSTRACT

Introduction: Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa treated patients with PD and motor fluctuations.

Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD.

Expert commentary: Oral OPC exhibits linear, dose-dependent absorption. However, following concomitant ingestion of a high-fat, high-calorie meal, the maximum plasma concentration will be decreased. A once-daily bedtime administration of OPC 1 h after the last daily L-Dopa/AADCi, are considered to avoid any interaction during the L-Dopa absorption phase. There are no clinically relevant effects of age (in adults), renal impairment or race on the pharmacokinetics of OPC. OPC dose adjustment is not needed in patients with mild to moderate chronic hepatic impairment. Opicapone exhibits the lowest potential for cytotoxicity in comparison with other COMT inhibitors. It significantly decreases COMT activity, with half-life of COMT inhibition in human erythrocytes of 61.6 h and increases systemic exposure to L-Dopa. This provides an enhancement in L-Dopa availability that translates into clinical benefit for PD patients in terms of significant decrease of OFF periods and increase in ON-time without troublesome dyskinesia.

KEYWORDS:

• Opicapone
• COMT inhibition
• L-DOPA
• Parkinson’s disease
• pharmacokinetic
• motor fluctuations

Box 1. Drug Summary Box.

Declaration of interest

V. S. Kostić has received research support from the Ministry of Education, Science and Technological Development of Republic of Serbia and from the SASA project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Ministry of Education, Science and Technological Development of the Republic of Serbia grant number 175090 and the SASA project.