Comparative Pharmacokinetics and Bioequivalence Evaluation of Two Formulations of Pramipexole Dihydrochloride Extended-Release Tablets in Healthy Chinese Subjects Under Fasted and Fed States: A Randomized, Open-Label, Single-Dose, Two-Period Crossover Clinical Trial

Background: Pramipexole dihydrochloride extended-release tablet is a novel long-acting form of non-ergot dopamine agonist indicated as one of main therapeutic approaches for Parkinson's disease. However, pharmacokinetic properties of extended-release pramipexole in healthy Chinese subjects remain unclear. Methods: A single-center, randomized, open-label, two-period crossover, single-dose study was performed to investigate comparative pharmacokinetics and evaluate bioequivalence of 0.375 mg test (Yangtze River Pharmaceutical Group Co., Ltd.) and reference (Trade name: Sifrol (R), Boehringer Ingelheim Pharma GmbH & Co. KG) formulations of pramipexole dihydrochloride extended-release tablets in healthy Chinese subjects under fasted and fed states. Results: A total of 56 subjects (28 in each dietary trial) were enrolled and randomized. After single dose of 0.375 mg test and reference formulations under fasted condition, main pharmacokinetics of pramipexole were as follows: peak concentration (C-max) were 409.33 +/- 95.93 and 413.77 +/- 132.03 pg/mL; plasma area under concentration-time curve from time 0 to last measurable concentration (AUC(0-t)) were 8801.95 +/- 1966.83 and 8646.37 +/- 2600.49 h*pg/mL; AUC from time 0 to infinity (AUC(0-infinity)) were 9469.03 +/- 1991.61 and 9082.95 +/- 2666.26 h*pg/mL; elimination half-life (t(1/2)) were 11.98 +/- 3.91 and 9.85 +/- 2.63 h; both time to reach C-max (T-max) were about 4.50 h, respectively, for test and reference formulations. The 90% confidence intervals of geometric mean ratios (test/reference) of C-max, AUC(0-t) and AUC(0-infinity) under fasted and fed conditions were all within 80-125%. Following administration under fed condition, C(ma)x and T-max for both test and reference formulations slightly increased and prolonged to 5.0 h, respectively, but AUC approximately remained unchanged compared with dosing under fasted condition. Test and reference formulations showed similar bioequivalence and favorable safety under fasted and fed states. Conclusion: Test and reference formulations of pramipexole dihydrochloride extended-release tablets (0.375 mg) showed similar bioequivalence and well safety and tolerability in healthy Chinese subjects under fasted and fed states, which supports further investigations of test formulation in patients with Parkinson's disease.

Automated summary

This study aimed to investigate the pharmacokinetics and bioequivalence of pramipexole dihydrochloride extended-release tablets in healthy Chinese subjects. The results showed that the test and reference formulations had similar pharmacokinetic properties in terms of peak concentration, time to reach peak concentration, and area under the curve. Therefore, the extended-release tablets demonstrated bioequivalence and safety in Chinese subjects.