Pharmacokinetic Interactions Between Pelubiprofen and Eperisone 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 treatment. 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 noncompartmental 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/m²) were enrolled, and 23 participants completed the study. For pelubiprofen, the geometric mean ratios (90% CIs) of C_max and AUC_0–∞ 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–∞ 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–∞ 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. Implications No clinically significant changes were noted in the pharmacokinetic interactions of pelubiprofen, the major active metabolite of pelubiprofen (trans-alcohol pelubiprofen), and eperisone hydrochloride between monotherapy and combination therapy with 45-mg sustained-release pelubiprofen and 75-mg sustained-release eperisone hydrochloride.