title: Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen.
abstract: OBJECTIVE
  Prostaglandin E2(PGE2) synthesis is modulated by COX2. Changes in PGE2could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects.
  
  
  METHODS
  A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2was applied to the pharmacodynamic evaluation.
  
  
  RESULTS
  After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration-time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%.
  
  
  CONCLUSIONS
  Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.
authors.affiliation: Clinical Trials Center, Gachon University Gil Medical Center, Incheon.
authors.forename: Dongseong
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Rehabilitation Medicine.
authors.forename: Sook Joung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea.
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Ha
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea.
authors.forename: Young-Sim
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea.
authors.forename: Se-Rin
authors.initials: SR
authors.lastname: Park
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea.
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Park
mesh_terms: D065567:Absorption, Physiological; D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004339:Drug Compounding; D064368:Healthy Volunteers; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D012995:Solubility; D055815:Young Adult
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007052:Ibuprofen
keywords: COX2-inhibitory effects; different formulation; ibuprofen