Pharmacokinetics and Tolerability of Entacapone, Levodopa, and Carbidopa Tablets in Healthy Chinese Subjects: A Randomized, Open-Label, Four-Period Crossover Study Under Fasting and Fed Conditions.

This study aimed to assess the pharmacokinetics, bioequivalence, and safety of a generic entacapone/levodopa/carbidopa (100/25/200 mg) tablet formulation compared to its reference listed drug (RLD, Stalevo) in healthy Chinese adults. A randomized, open-label, single-dose, four-period crossover study was conducted under fasting and fed conditions, with a 5-day washout. A total of 68 subjects were enrolled and randomly assigned (1:1) to receive a single oral dose of either the test or reference formulation. Plasma concentrations of analytes were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and key pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) were calculated. Under both fasting and fed conditions, bioequivalence was assessed under both fasting and fed conditions using the reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) approach. For the key pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞), the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) all fell within the 80.00%-125.00% range, or the one-sided 95% upper confidence bound for the scaled difference was ≤0 and the point estimate of the GMR between the test and reference formulations fell within the 80.00%-125.00% range, thus confirming bioequivalence. Concomitant high-fat food intake had a certain impact on the pharmacokinetics of each active ingredient. Adverse events (AEs) were mild, with no serious AEs reported, indicating comparable safety profiles. In conclusion, the generic formulation is bioequivalent to the RLD and demonstrates an acceptable safety profile in healthy Chinese subjects.