Pharmacokinetics of oral pridinol: Results of a randomized, crossover bioequivalence trial in healthy subjects

Objectives: To establish the relative bioavailability and to assess bioequivalence of oral, immediate-release tablets containing pridinol and to determine the pharmacokinetic properties of the compound. Methods and materials: In this single-center, open-label, randomized, crossover trial, healthy male and female adult subjects received single doses of the test and reference product containing 4 mg pridinol mesylate (equivalent to 3 mg pridinol) each under fasting conditions. For pharmacokinetic evaluation, blood samples were withdrawn until 72 hours post dose. Pridinol in plasma was quantified by validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Adverse events (AEs) were analyzed descriptively. Results: Of 34 randomized subjects, 33 completed all treatments. The determined pharmacokinetic parameters were quite similar for both products, with geometric means for maximum exposure (C-max) of 29.27 ng/mL (test) and 27.44 ng/mL (reference), reached after 1.00 and 0.90 hours (mean t(max)), respectively. The extents of bioavailability (geometric mean AUC(0-tlast)) were 187.93 hxng/mL (test) and 183.51 hxng/mL (reference). Elimination half-lives (T-1/2) ranged from 8.97 to 34.85 hours with comparable mean T-1/2 of 19.14 hours (test) and 18.85 hours (reference). The point estimates of the test/reference-adjusted geometric mean ratios of AUC(0-tlast), C-max (primary), and AUC(0-infinity) (secondary) were 102.54% (90% confidence interval: 96.19 - 109.32%), 106.79% (99.00 - 115.20%), and 102.60% (96.20 - 109.43%), respectively. Overall, 23 subjects experienced 50 AEs; headache and dizziness (15 cases each) were most frequently reported. Conclusion: Bioequivalence of both pridinol products was demonstrated in terms of rate and extent of absorption. Safety and tolerability were in accordance with the known AE profile of the drug substance.