Pharmacokinetics and Bioavailability of Naprosyn Cr 500 Mg Tablet, a New Controlled-Release Formulation of Naproxen, After Single and Multiple Dosing

Naprosyn CR 500 mg, a new controlled-release (CR) tablet formulation of naproxen, is suggested for use once daily for the treatment of arthritic diseases. The aim of this study was to evaluate the bioavailability (F) and pharmacokinetics of 500 mg CR tablets using standard Naprosyn (2 x 250 mg) tablets as the reference standard. A random crossover design was used in 15 healthy male volunteers. In phase I, the subjects ingested either one 500 mg CR tablet in the morning or one 250 mg Naprosyn tablet in the morning followed by one 250 mg standard Naprosyn tablet 12 h later. The plasma naproxen concentration-time profile was monitored for 48 h from the time of the initial dose. From day 3 the subjects continued to take the same formulation for 5 days. On day 8 a further 72 h of blood sampling was started (phase II). After a 5-day washout period subjects returned and the 9-day procedure was repeated using the other formulation. In phase I of the study, mean values of maximum plasma naproxen concentration (C(max)) for the standard Naprosyn tablets after the morning and evening doses were 39.3 and 44.7-mu-g ml-1, respectively, and were significantly higher than the mean C(max) (33.6-mu-g ml-1) for CR tablets (P < 0.01). The time to maximum plasma naproxen concentration (t(max)) for standard Naprosyn tablet averaged 2.5 and 3.1 h after the morning and evening doses, respectively. The mean t(max) for the CR tablets was 9.8 h and was significantly greater than the values for the standard Naprosyn tablets. The total area under the plasma concentration-time curve (AUC0-infinity) was not significantly different between these two formulations after the single dose study. The mean elimination half-lives were 15.2 and 15.3 h for the standard Naprosyn tablets and the CR tablets, respectively. In phase II of the study, the mean C(max) values for the 250 mg Naprosyn tablets were 64.2 and 55.4-mu-g ml-1 after the morning and evening doses, respectively and the C(max) was 52.6-mu-g ml-1 for the 500 mg CR tablets. The mean t(max) for the CR tablets (6.0 h) was greater than that for the Naprosyn tablets (2.2 and 3.7 h). The relative F of the 500 mg CR tablets assessed during the dose interval at steady-state was, on average, 96% of the 250 mg Naprosyn tablets