title: 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.
abstract: BACKGROUND
  A new controlled-release formulation of aceclofenac 200 mg (Clanza CR®) developed by Korea United Pharm., Inc., South Korea, for once-daily (od) dosing provides biphasic aceclofenac release consisting of immediate release of 85 mg 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 (100 mg 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 treatment-period, crossover, single-centre study with a 1-week washout in 41 healthy adults. The three treatments consisted of immediate-release aceclofenac 100 mg bid administered under fasting conditions; controlled-release aceclofenac 200 mg od administered under fasting conditions; and controlled-release aceclofenac 200 mg od administered immediately after a standardized high-fat breakfast. Plasma concentrations of aceclofenac were determined using a high-performance liquid chromatography method.
  
  
  RESULTS
  In the fasted state, the 90% confidence intervals (CIs) of the least squares geometric mean ratios (GMRs) for the area under the plasma concentration-time curve from time zero to 24 hours (AUC(24)) and the peak plasma concentration (C(max)) 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 AUC(24) and C(max) 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.
  
  
  CONCLUSIONS
  The results demonstrate that controlled-release aceclofenac 200 mg is equivalent to immediate-release aceclofenac 100 mg when administered at the same total daily dose. Additionally, the bioavailability of controlled-release aceclofenac was not affected by high-fat foods.
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon, South Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Soo-Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Seong
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Shin
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lim
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004041:Dietary Fats; D004334:Drug Administration Schedule; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D056910:Republic of Korea; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D004008:Diclofenac; C056498:aceclofenac