{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:20:36Z","timestamp":1753878036716,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T00:00:00Z","timestamp":1721520000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>JBPOS0101 is a new antiepileptic drug and is a substrate of UDP\u2010glucuronosyltransferases (UGTs) in in\u00a0vitro test. In\u00a0vitro experiments showed different results regarding whether JBPOS0101 induces (EC<jats:sub>50<\/jats:sub> 136\u2009\u03bcM) or inhibits (IC<jats:sub>50<\/jats:sub> 95.4\u2013386.5\u2009\u03bcM) cytochrome P450 (CYP) 3A4. As co\u2010medication of JBPOS0101 and carbamazepine (CBZ) is expected in clinical settings, drug\u2013drug interactions (DDIs) between them should be determined. This study aimed to investigate pharmacokinetic (PK) interactions of JBPOS0101 influenced by CYP3A4 and UGTs using midazolam (MDZ) and CBZ. A two\u2010cohort, open\u2010label, fixed\u2010sequence study was conducted in healthy Koreans. In cohort A, subjects received MDZ IV alone, and then JBPOS0101 were co\u2010administered with MDZ after oral doses of JBPOS0101 for 7\u2009days. In cohort B, multiple doses of JBPOS0101 and CBZ were administered respectively, and subjects received both together for 7\u2009days. Serial blood samples were collected for PK analysis. When MDZ and JBPOS0101 were co\u2010administered, the systemic exposure of MDZ decreased by 30%. Meanwhile, JBPOS0101 did not significantly changed the PK of CBZ. CBZ decreased the systemic exposure of JBPOS0101 at steady state by 40%, respectively. With IV administration of MDZ, JBPOS0101 acted as a weak inducer of hepatic CYP3A4 and decreased systemic exposure of MDZ. The ability of JBPOS0101 to similarly modulate gut CYP3A4 activity will require further evaluation. Co\u2010administration of multiple doses of JBPOS0101 and CBZ did not significantly alter CBZ pharmacokinetics, but the clinical impact of decreased systemic exposure of JBPOS0101 by CBZ should be further considered.<\/jats:p>","DOI":"10.1111\/cts.13892","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T04:19:53Z","timestamp":1721621993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic drug\u2013drug interactions of JBPOS0101 mediated by cytochrome P450 3A4 and UDP\u2010glucuronosyltransferases"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0154-5777","authenticated-orcid":false,"given":"Sejung","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"},{"name":"Kidney Research Institute Seoul National University Medical Research Center  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Moon","family":"Choi","sequence":"additional","affiliation":[{"name":"Bio\u2010Pharm Solutions Co. Ltd  Suwon Gyeonggi\u2010Do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung\u2010Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Bio\u2010Pharm Solutions Co. Ltd  Suwon Gyeonggi\u2010Do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-9194","authenticated-orcid":false,"given":"SeungHwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1371\/journal.pone.0237153"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1016\/j.ibror.2019.07.1201"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1016\/0006-2952(94)90543-6"},{"issue":"6","key":"e_1_2_10_5_1","article-title":"Midazolam as a probe for heterotropic drug\u2013drug interactions mediated by CYP3A4","volume":"12","author":"Denisov IG","year":"2022","journal-title":"Biomol Ther"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1007\/s00228-017-2282-7"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1038\/nrdp.2018.24"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1007\/s40263-021-00827-8"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.2165\/00003088-199631030-00004"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.1016\/j.yebeh.2020.107261"},{"unstructured":"International Council for Harmonisation.ICH Guideline M12 on drug interaction studies Step 2b.2022Accessed July 19 2023.https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/draft\u2010ich\u2010guideline\u2010m12\u2010drug\u2010interaction\u2010studies\u2010step\u20102b_en.pdf","key":"e_1_2_10_11_1"},{"unstructured":"US Food and Drug Administration (FDA).Clinical Drug Interaction Studies \u2013 Cytochrome P450 Enzyme\u2010 and Transporter\u2010 Mediated Drug Interactions.2020Accessed July 19 2023.https:\/\/www.fda.gov\/media\/134581\/download","key":"e_1_2_10_12_1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1111\/j.1528-1167.2012.03671.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.9740\/mhc.2015.01.008"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1111\/cts.13344"},{"unstructured":"US Food and Drug Administration (FDA).In vitro drug interaction studies cytochrome P450 enzyme and transporter mediated drug interactions. 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