PII-066 - PHARMACOKINETIC AND PHARMACODYNAMIC CHARACTERISTICS OF PELUBIPROFEN TROMETHAMINE VERSUS PELUBIPROFEN IN HEALTHY SUBJECTS.
Thursday, March 23, 2023
5:00 PM – 6:30 PM EDT
H. Kim1, Y. Son1, Y. Jang1, Y. Choi1, Y. Lee1, H. Min1, J. Seo2, S. Jeong1, M. Park1, Y. Kim1; 1Chungbuk National University Hospital, Cheong-ju, Republic of Korea, 2Daewon Pharmaceutical Co., Ltd., Seoul, Republic of Korea.
Chungbuk National University Hospital, United States
Background: Compared to pelubiprofen, a cyclooxygenase-2 (COX-2) selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. This study was aimed to assess the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of pelubiprofen and pelubiprofen tromethamine. Methods: Two independent clinical trials were performed in healthy subjects using a randomized, single-dose, two-treatment, two-sequence, four-period crossover design. In each study (Study I and II), 36 subjects were randomized to receive 25 mg or 30 mg pelubiprofen tromethamine with 30 mg pelubiprofen being the reference. Serial blood samplings for plasma pelubiprofen were performed up to 8 h. For PK evaluation, the geometric mean ratios (GMR) and the 90% confidence interval (90% Cl) of maximum concentration (Cmax) and area under the time versus concentration curve from time 0 to the last measurable timepoint (AUC0-t) were analyzed. For PD evaluation, following 24 h of Lipopolysaccharide response, the plasma Prostaglandin E2 concentrations in Study I were determined using Enzyme-Linked Immunosorbent Assay. Results: The GMR (90% CI) of 25 mg pelubiprofen tromethamine versus reference in Study I were 1.1558 (1.0197-1.3101) and 1.0674 (1.0187-1.1184) for Cmax and AUC0-t, respectively. A trend of increased absorption and exposure for 30 mg pelubiprofen tromethamine versus reference in Study II was observed. The maximum COX-2 inhibitory effect of 25 mg pelubiprofen tromethamine was 98% compared to the reference, showing no significant PD variation. Conclusion: It is thus predicted that 25 mg pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg pelubiprofen.