Pharmacokinetics of a new once-daily controlled-release formulation of aceclofenac in korean healthy subjects compared with immediate-release aceclofenac and the effect of food: A randomized, open-label, three-period, crossover, single-centre study

Background: A new controlled-release formulation of aceclofenac 200mg (Clanza CR®) developed by Korea United Pharm., Inc., South Korea, for once-daily (od) dosing provides biphasic aceclofenac release consisting of immediate release of 85mg followed by sustained release of 115 mg. Food has been known to affect the rate and extent of absorption of several drugs, in both immediate-release and controlled-release formulations. Objective: The aim of this study was to evaluate the relative bioavailability of a new controlled-release formulation of aceclofenac (200 mg od; Clanza CR®) in comparison with immediate-release aceclofenac (100mg twice daily [bid], Airtal®) and to assess the effect of food on the pharmacokinetics of the new controlled-release aceclofenac formulation. Methods: This study was designed as a randomized, open-label, three treatmentperiod, crossover, single-centre study with a 1-week washout in 41 healthy adults. The three treatments consisted of immediate-release aceclofenac 100mg bid administered under fasting conditions; controlled-release aceclofenac 200mg od administered under fasting conditions; and controlled-release aceclofenac 200mg od administered immediately after a standardized high-fat breakfast. Plasma concentrations of aceclofenac were determined using a highperformance liquid chromatography method. Results: In the fasted state, the 90%confidence intervals (CIs) of the least squares geometricmean ratios (GMRs) for the area under the plasma concentration-time curve from time zero to 24 hours (AUC24) and the peak plasma concentration (Cmax) of aceclofenac for the controlled-release and immediate-release formulations of aceclofenac were all within the bioequivalence criteria range of 0.8-1.25. The 90% CIs of the GMRs for the AUC24 and Cmax of aceclofenac for the controlled-release formulation of aceclofenac in the fed and fasted states were also within the bioequivalence range. Both aceclofenac formulations were well tolerated in all subjects, and no serious adverse effects were observed. Conclusion: The results demonstrate that controlled-release aceclofenac 200mg is equivalent to immediate-release aceclofenac 100mg when administered at the same total daily dose. Additionally, the bioavailability of controlled-release aceclofenac was not affected by high-fat foods.