Pharmacokinetic Interactions Between Pelubiprofen and Eperis one Hydrochloride: A Randomized, Open-label, Crossover Study of Healthy Korean Men

Purpose: Pelubiprofen is a novel nonsteroidal anti-inflammatory, analgesic, and antipyretic drug with at least similar efficacy and better tolerability compared with other nonsteroidal anti-inflammatory, analgesic, and antipyretic drugs such as naproxen and aceclofenac. Eperisone hydrochloride is a centrally acting muscle relaxant that performs by blocking calcium channels. The combined use of pelubiprofen and eperisone hydrochloride is increasingly anticipated to promote the clinical effectiveness of pelubiprofen in relieving musculoskeletal symptoms of osteoarthritis, rheumatoid arthritis, and low back pain. No published data are yet available, however, regarding the pharmacokinetic interactions between these 2 drugs when administered concurrently. The objective of this study was to evaluate any pharmacokinetic interactions between pelubiprofen and eperisone hydrochloride in healthy Korean male volunteers. Methods: This was a randomized, open-label, crossover study. Each participant was randomly assigned to 1 of 6 treatment sequences and orally received either 45 mg sustained-release pelubiprofen, 75-mg sustained-release eperisone hydrochloride, or both as a single dose in each treatment period, with a 7-day washout period between each trealnient. Serial blood samples were collected over 24 hours after dosing, and plasma concentrations of each drug and the major active metabolite of pelubiprofen (trans-alcohol pelubiprofen) were determined by using a validated HPLC-MS/MS system. Pharmacokinetic analyses were conducted by using non-compartmental methods. Findings: A total of 24 men (mean +/- standard deviation of: age, 29 +/- 4 years; weight, 72.5 +/- 7.8 kg; body mass index, 23.4 +/- 1.9 kg/m(2)) were enrolled, and 23 participants completed the study. For pelubiprofen, the geometric mean ratios (90% CIs) of C-max and AUC(0-infinity) were 1.02 (0.87-1.19) and 0.97 (0.88-1.07), respectively. For the major active metabolite of pelubiprofen (trans-alcohol pelubiprofen), the geometric mean ratios (90% CIs) of C-max. and AUC(0-infinity) were 1.05 (0.98-1.13) and 1.04 (1.01-1.07). For eperisone, the geometric mean ratios (90% CIs) of C-max and AUC(0-infinity), were 0.87 (0.67-1.15) and 1.05 (0.85-1.30). None of the study participants experienced serious adverse events during the study. (C) 2017 Elsevier HS Journals, Inc. All rights reserved.