Bioequivalence of 2 Naproxen Sodium Tablet Formulations in Healthy Male and Female Volunteers

Abstract

ABSTRACT: Background: Naproxen is an established, effective treatment for pain management in acute musculoskeletal disorders and traumatic sports injuries. Reckitt Benckiser Health Limited have developed a naproxen sodium tablet with the same pharmacokinetic and pharmacodynamic properties as existing marketed naproxen products with the intention of increasing the number of naproxen products available for prescribers and pharmacies. Objective: This study aimed to assess comparative bioavailability between a test medicinal product developed by Reckitt Benckiser Health Limited (RB, 103-105 Bath Rd, Slough, SL1 3UH, United Kingdom; RB naproxen sodium 220 mg tablets), and a reference medicinal product, Aleve naproxen sodium 220 mg (Bayer B.V., Energieweg 1, 3641 RT Mijdrecht, Netherlands), in the fasted state. Methods: This was a randomized, single-dose, 2-way crossover, open-label, comparative bioavailability, pharmacokinetic study in 18 healthy male and female volunteers with a 5- to 8-day washout permitted between doses (based on the anticipated minimum washout period for naproxen determined from the known terminal elimination half-life of up to 17 hours). Blood samples were taken periodically over a 72-hour period following dosing and analyzed for plasma naproxen concentration using a validated LC-MS method. Noncompartmental pharmacokinetic analysis was used to derive pharmacokinetic parameters for naproxen; safety and tolerability were evaluated throughout the study. Results: Following a single-dose administration of naproxen sodium tablets (2 × 220 mg), the Cmax and AUC0–t (geometric least squares mean) for the test product was 65.88 µg/mL and 893.37 h * µg/mL, respectively; and for the reference product was 64.59 µg/mL and 890.60 h * µg/mL. The geometric least squares mean test/reference ratio 90% CI for both Cmax (93.98–110.70) and AUC0–t (98.04–102.63) was contained entirely within the predefined 80.00% to 125.00% lower and upper limits; additionally, there was no statistically significant difference in Tmax (P = 0.9878) following fasted administration of the test and reference product. There was 1 treatment-emergent adverse event reported during the study; there were no serious adverse events, no suspected unexpected serious adverse events, and no clinically significant changes in laboratory safety, vital signs, or 12-lead ECG measurements reported. Conclusions: This single-dose study found that the test product (RB naproxen sodium tablets) and reference product (Aleve naproxen sodium tablets) met the regulatory criteria for bioequivalence in these fasted male and female volunteers; both test and reference products were found to be safe and well tolerated. Key words: Anti-inflammatory drug, Bioequivalence, Naproxen, Nonsteroidal, Pain management, Classification: pharmacokinetics, pain management