title: Pharmacokinetic Interactions Between Pelubiprofen and Eperisone Hydrochloride: A Randomized, Open-label, Crossover Study of Healthy Korean Men.
abstract: 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.
  
  
  
  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.
  
  
  
  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 Cmaxand AUC0-∞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 Cmaxand AUC0-∞were 1.05 (0.98-1.13) and 1.04 (1.01-1.07). For eperisone, the geometric mean ratios (90% CIs) of Cmaxand AUC0-∞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.
  
  
  
  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.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, South Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, South Korea; Daewon Pharm Co, Ltd, Kwangjin-ku, Seoul, South Korea.
authors.forename: Joo-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Daewon Pharm Co, Ltd, Kwangjin-ku, Seoul, South Korea.
authors.forename: Hyung Son
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Gyu-Jeong
authors.initials: GJ
authors.lastname: Noh
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, South Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, South Korea. Electronic address: ktlee@khu.ac.kr.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, South Korea. Electronic address: cekchung@khu.ac.kr.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Chung
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D010666:Phenylpropionates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011427:Propiophenones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D010666:Phenylpropionates; D011427:Propiophenones; C040375:pelubiprofen; C030848:eperisone
keywords: drug interactions; eperisone; pelubiprofen; pharmacokinetics