Pharmacokinetics of oral pridinol: Results of a randomized, crossover bioequivalence trial in healthy subjects
| Autor: | André Warnke, Frank Donath, Ralph-Steven Wedemeyer, Maren Richter, Andreas Horstmann, Claudia Peschel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Cmax Administration Oral immediate-release tablet Bioequivalence Gastroenterology Piperidines Pharmacokinetics Tandem Mass Spectrometry Internal medicine Humans Medicine Pharmacology (medical) Pridinol Pharmacology bioequivalence Cross-Over Studies business.industry Crossover study Healthy Volunteers Bioavailability pridinol Therapeutic Equivalency Tolerability Area Under Curve Female Geometric mean bioavailability business pharmacokinetics Research Article Chromatography Liquid Tablets medicine.drug |
| Zdroj: | International Journal of Clinical Pharmacology and Therapeutics |
| ISSN: | 0946-1965 |
| Popis: | 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 For pharmacokinetic evaluation, blood samples were withdrawn until 72 hours post dose.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 (Cmax) of 29.27 ng/mL (test) and 27.44 ng/mL (reference), reached after 1.00 and 0.90 hours (mean tmax), respectively. The extents of bioavailability (geometric mean AUC0-tlast) were 187.93 h×ng/mL (test) and 183.51 h×ng/mL (reference). Elimination half-lives (T1/2) ranged from 8.97 to 34.85 hours with comparable mean T1/2 of 19.14 hours (test) and 18.85 hours (reference). The point estimates of the test/reference-adjusted geometric mean ratios of AUC0-tlast, Cmax (primary), and AUC0-∞ (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. |
| Databáze: | OpenAIRE |
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