Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen

• Published in: Drug design, development and therapy development and therapy, 2017-01, Vol.11, p.135-141
• Main Authors: Shin, Dongseong, Lee, Sook Joung, Ha, Yu-Mi, Choi, Young-Sim, Kim, Jae-Won, Park, Se-Rin, Park, Min Kyu
• Format: Article
• Language: English
• Subjects: Absorption; Absorption, Physiological; Administration, Oral; Adult; Analysis; Arginine; Bioavailability; Chromatography; COX-2 inhibitory effects; Cross-Over Studies; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacokinetics; Cyclooxygenase-2; Cyclooxygenases; different formulation; Dinoprostone - antagonists & inhibitors; Dinoprostone - metabolism; Dosage and administration; Drug Compounding; Drug dosages; Drug therapy; Evaluation; Formulations; Health aspects; Healthy Volunteers; Humans; Ibuprofen; Ibuprofen - administration & dosage; Ibuprofen - chemistry; Ibuprofen - pharmacokinetics; Inhibition; Laboratories; Lipopolysaccharides; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Male; Middle Aged; Nonsteroidal anti-inflammatory drugs; Original Research; Pain; Pharmacodynamics; Pharmacokinetics; Pharmacological research; Pharmacology; Physiological aspects; Prostaglandin E2; Prostaglandin synthesis; Republic of Korea; Rheumatoid arthritis; Solubility; Tablets; University colleges; Young Adult
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S121633

Prostaglandin E (PGE ) synthesis is modulated by COX2. Changes in PGE could 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. 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 PGE inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE was applied to the pharmacodynamic evaluation. 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 PGE WAI 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%. 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.