{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:50:27Z","timestamp":1791528627749,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ojeok\u2010san is a traditional multiherbal formulation commonly prescribed for musculoskeletal symptoms in East Asian medicine. The concomitant use of herbal medicines and conventional pharmacotherapy is common in patients with musculoskeletal disorders; however, the pharmacokinetic (PK) interactions between eperisone and ojeok\u2010san have not been evaluated. This was an open\u2010label, randomized, single\u2010dose, three\u2010treatment, six\u2010sequence, three\u2010period crossover study designed to evaluate the PK interactions between eperisone and ojeok\u2010san in 24 healthy male participants. In each period, participants received a single oral dose of 150\u00a0mg eperisone, 15.0\u00a0g ojeok\u2010san, or 150\u00a0mg eperisone plus 15.0\u00a0g ojeok\u2010san, with 7\u2010day washout periods between treatments. Plasma concentrations of eperisone and ephedrine, a marker constituent of ojeok\u2010san, were quantified using validated liquid chromatography\u2013tandem mass spectrometry. Coadministration with ojeok\u2010san reduced eperisone exposure, with geometric mean ratios (GMRs) for C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>last<\/jats:sub>\n                    of 0.34 (90% CI: 0.25\u20100.46) and 0.51 (90% CI: 0.41\u20100.64), respectively. In contrast, eperisone had little effect on ephedrine exposure, with GMRs for C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>last<\/jats:sub>\n                    of 1.04 (90% CI: 0.98\u20101.09) and 1.12 (90% CI: 1.05\u20101.20), respectively. No adverse events were reported. These findings demonstrated a PK interaction in which ojeok\u2010san reduced systemic exposure to eperisone.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70111","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:20:37Z","timestamp":1791526837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic Interaction Between Eperisone and Ojeok\u2010San in Healthy Subjects"],"prefix":"10.1002","volume":"15","author":[{"given":"Do Hoon","family":"Keum","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Severance Hospital Yonsei University Health System Seoul Republic of Korea"},{"name":"Department of Pharmaceutical Medicine and Regulatory Sciences Colleges of Medicine and Pharmacy Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyu","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Severance Hospital Yonsei University Health System Seoul Republic of Korea"},{"name":"Department of Pharmaceutical Medicine and Regulatory Sciences Colleges of Medicine and Pharmacy Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Hoon","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Severance Hospital Yonsei University Health System Seoul Republic of Korea"},{"name":"Department of Pharmaceutical Medicine and Regulatory Sciences Colleges of Medicine and Pharmacy Yonsei University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukyong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Severance Hospital Yonsei University Health System Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Severance Hospital Yonsei University Health System Seoul Republic of Korea"},{"name":"Department of Pharmaceutical Medicine and Regulatory Sciences Colleges of Medicine and Pharmacy Yonsei University  Incheon Republic of Korea"},{"name":"Department of Pediatrics Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Korean Medicine Dongguk University  Gyeongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won\u2010Yung","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Korean Medicine Wonkwang University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon Ok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Severance Hospital Yonsei University Health System Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"4","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1007\/s00586-025-09440-5","article-title":"Global, regional, and national burden of disease in neck pain: statistical analysis of incidence, prevalence, and DALYs, with projections to 2036","volume":"35","author":"Zhu Y","year":"2026","journal-title":"Eur Spine J"},{"issue":"5","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0063209","article-title":"Use of traditional Korean medicine by patients with musculoskeletal disorders","volume":"8","author":"Wang BR","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.clinthera.2023.10.003","article-title":"Muscle strength decline caused by eperisone hydrochloride: a case report","volume":"46","author":"Zhu J","year":"2024","journal-title":"Clin Ther"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40122-020-00218-9","article-title":"Pharmacological management of adults with chronic non\u2010cancer pain in general practice","volume":"9","author":"Bonezzi C","year":"2020","journal-title":"Pain Ther"},{"issue":"3","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1124\/jpet.105.089805","article-title":"Tolperisone\u2010type drugs inhibit spinal reflexes via blockade of voltage\u2010gated sodium and calcium channels","volume":"315","author":"Kocsis P","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0022-3565(25)24210-0","article-title":"Eperisone, an antispastic agent, possesses vasodilating actions on the guinea\u2010pig basilar artery","volume":"235","author":"Fujioka M","year":"1985","journal-title":"J Pharmacol Exp Ther"},{"issue":"6","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1097\/BRS.0b013e318166e051","article-title":"The effect of muscle relaxant on the paraspinal muscle blood flow: a randomized controlled trial in patients with chronic low back pain","volume":"33","author":"Sakai Y","year":"2008","journal-title":"Spine (Phila Pa 1976)"},{"issue":"2","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s13318-011-0034-0","article-title":"Human pharmacokinetics of the muscle relaxant, eperisone hydrochloride by liquid chromatography\u2010electrospray tandem mass spectrometry","volume":"36","author":"Melilli B","year":"2011","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1038\/s41598-020-58801-1","article-title":"Comparative pharmacokinetics of osmotic\u2010controlled and immediate\u2010release eperisone tablet formulation in healthy human subjects using a sensitive plasma LC\u2010ESI\u2010MS\/MS method","volume":"10","author":"Ahmed K","year":"2020","journal-title":"Sci Rep"},{"issue":"2","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/bdd.2264","article-title":"Pharmacokinetics of eperisone following oral administration in healthy Korean volunteers","volume":"42","author":"Baek IH","year":"2021","journal-title":"Biopharm Drug Dispos"},{"issue":"1","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/00498250802509448","article-title":"Characterization of human cytochrome P450 enzymes involved in the biotransformation of eperisone","volume":"39","author":"Yoo HH","year":"2009","journal-title":"Xenobiotica"},{"issue":"8","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1023\/A:1010922925928","article-title":"Intestinal first\u2010pass metabolism of eperisone in the rat","volume":"18","author":"Mihara K","year":"2001","journal-title":"Pharm Res"},{"issue":"11","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1089\/acm.2011.0312","article-title":"Study to establish ojeok\u2010san (five accumulation powder: wu ji San) administration criteria and a questionnaire to evaluate the holistic effects of ojeok\u2010san on patients with low back pain","volume":"19","author":"Kim EJ","year":"2013","journal-title":"J Altern Complement Med"},{"issue":"6","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0270338","article-title":"Ojeok\u2010san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer","volume":"17","author":"Cunningham P","year":"2022","journal-title":"PLoS One"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fphar.2012.00069","article-title":"An overview of the evidence and mechanisms of herb\u2010drug interactions","volume":"3","author":"Fasinu PS","year":"2012","journal-title":"Front Pharmacol"},{"key":"e_1_2_10_17_1","article-title":"Pharmacokinetic interactions of herbs with cytochrome P450 and P\u2010glycoprotein","volume":"2015","author":"Cho HJ","year":"2015","journal-title":"Evid Based Complement Alternat Med"},{"issue":"1","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/bcpt.12971","article-title":"Effects of ojeok\u2010san on the pharmacokinetics of celecoxib at steady\u2010state in healthy volunteers","volume":"123","author":"Park SI","year":"2018","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"7825","DOI":"10.2147\/DDDT.S526915","article-title":"Pharmacokinetic and pharmacodynamic interaction of metformin and ojeok\u2010san in healthy volunteers","volume":"19","author":"Lee S","year":"2025","journal-title":"Drug Des Devel Ther"},{"issue":"23","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222312808","article-title":"Cytochrome P450 enzymes and drug metabolism in humans","volume":"22","author":"Zhao M","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"2","key":"e_1_2_10_21_1","first-page":"33","article-title":"A short introduction to pharmacokinetics","volume":"6","author":"Urso R","year":"2002","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"2","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/jps.2600830219","article-title":"Evaluation of different indirect measures of rate of drug absorption in comparative pharmacokinetic studies","volume":"83","author":"Lacey LF","year":"1994","journal-title":"J Pharm Sci"},{"issue":"5","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.2174\/1389200211209050640","article-title":"Herb\u2010drug interactions and mechanistic and clinical considerations","volume":"13","author":"Chen XW","year":"2012","journal-title":"Curr Drug Metab"},{"issue":"3","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2125.2005.02254.x","article-title":"Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects","volume":"59","author":"Csajka C","year":"2005","journal-title":"Br J Clin Pharmacol"},{"issue":"5","key":"e_1_2_10_25_1","first-page":"365","article-title":"Efficacy and tolerability of eperisone in patients with spastic palsy: a cross\u2010over, placebo\u2010controlled dose\u2010ranging trial","volume":"13","author":"Bresolin N","year":"2009","journal-title":"Eur Rev Med Pharmacol Sci"}],"container-title":["Clinical Pharmacology in Drug 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History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70111"}}