Objective: Few studies have examined levodopa (LD) pharmacokinetics in combination with opicapone (OPC) in Japanese patients with Parkinson’s disease (PD). Therefore, we investigated changes in LD pharmacokinetics when OPCs were combined with a fixed-dose combination of LD/dopa decarboxylase inhibitor (DCI) in order to implement a rational prescribing design when OPCs are used.
Background: The mainstay of PD treatment is dopamine replacement therapy with LD formulations, which have a low bioavailability and short half-life, and are combined with LD metabolizing enzyme inhibitors to deliver LD more efficiently into the brain. OPC was launched in 2020 as a peripheral catechol-O-methyltransferase (COMT) inhibitor also in Japan. COMT inhibitors inhibit the metabolism of LD to 3-O -methyldopa (3-OMD), which is expected to increase the Area Under the Curve (AUC) of LD and decrease the metabolite 3-OMD.
Method: The pharmacokinetics of LD and its metabolites during oral administration of fixed-dose LD/DCI and their respective AUCs with OPC 25 mg were studied in 8 PD patients (4 males and 4 females) hospitalized in our facility. LD and its metabolites were measured using High Performance Liquid Chromatography (HPLC).
Results: When OPCs were added during oral administration of the LD/DCI fixed-dose combination, the AUC for LD increased to 1.3 (0.15) (mean (SD))-fold and the AUC for 3-OMD decreased 0.33 (0.13)-fold; the effect of OPCs on LD varied from 1.10 to 1.71-fold between individuals.
Pharmacokinetics in non-Japanese subjects showed that concomitant OPCs increased the AUC of LD by about 1.5-fold, but the rate of increase in AUC of LD in the present study was less than previously reported.
Conclusion: The pharmacokinetics of LD and its metabolites were investigated in Japanese PD patients when OPC was concomitantly administered during oral administration of a fixed-dose combination of LD and DCI; the AUC of LD increased 1.3-fold and that of 3-OMD decreased 0.33-fold with OPC concomitant administration. It was considered possible that the COMT inhibitor may be less effective in this study because DCI with low DCI content is often used in Japan. It is also possible that responder and non-responder to COMT inhibitors are mixed, and it is necessary to examine the relationship between the amount of effect and genetic polymorphism of the COMT gene in the future.
To cite this abstract in AMA style:
D. Kamiyama, N. Nishikawa, G. Oyama, T. Hatano, N. Hattori. The effect of co-administration of opicapone on the pharmacokinetics of levodopa [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/the-effect-of-co-administration-of-opicapone-on-the-pharmacokinetics-of-levodopa/. Accessed September 7, 2024.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-co-administration-of-opicapone-on-the-pharmacokinetics-of-levodopa/