{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T10:45:54Z","timestamp":1749206754648,"version":"3.40.4"},"reference-count":32,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ningbo Medical & Health Leading Academic Discipline Project","award":["No. 2022-Z03"],"award-info":[{"award-number":["No. 2022-Z03"]}]},{"name":"Ningbo Medical & Health Brand Discipline Project","award":["No. PPXK2024-08"],"award-info":[{"award-number":["No. PPXK2024-08"]}]},{"name":"APC: Traditional Chinese Medicine Pharmaceutical Center Construction Project","award":["No. zyy23011"],"award-info":[{"award-number":["No. zyy23011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Bedaquiline has recently been approved for the treatment of multidrug-resistant tuberculosis. Carvedilol is a cardiovascular medication extensively used in the treatment of heart failure and hypertension. In this study, Sprague-Dawley rats, rat liver microsomes (RLM), human liver microsomes (HLM), and recombinant human CYP3A4 were used to explore the effect of carvedilol on the metabolism of bedaquiline. Ultra-performance liquid chromatography-tandem mass spectrometry was used to facilitate the quantification of the analyte concentrations. <jats:italic>In vitro,<\/jats:italic> carvedilol did not exhibit time-dependent inhibition of bedaquiline, which aligns with the half-maximal inhibitory concentration (IC<jats:sub>50<\/jats:sub>) shift results. The IC<jats:sub>50<\/jats:sub> values of carvedilol were 15.35 \u00b1\u00a00.43 \u00b5M in RLM, 7.55 \u00b1\u00a00.74 \u00b5M in HLM, and 0.79 \u00b1\u00a00.05 \u00b5M in CYP3A4. Besides, the inhibition type of carvedilol was found to be mixed, un-competitive, and mixed in RLM, HLM, and CYP3A4, respectively. <jats:italic>In vivo<\/jats:italic>, the co-administration of carvedilol with bedaquiline resulted in a significant increase in the area under the plasma concentration-time curve (AUC)<jats:sub>(0\u00a0\u2212\u00a0<jats:italic>t<\/jats:italic>)<\/jats:sub>, AUC<jats:sub>(0\u00a0\u2212\u00a0\u221e),<\/jats:sub> and C<jats:sub>max<\/jats:sub> of bedaquiline while decreasing its CL<jats:sub>z\/F<\/jats:sub>. <jats:bold>Lay summary<\/jats:bold>: Carvedilol could inhibit the metabolism of bedaquiline <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, with different mechanisms in different enzymatic reaction systems. Hence, caution should be exercised when combining bedaquiline with carvedilol.<\/jats:p>","DOI":"10.7717\/peerj.19313","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T08:23:52Z","timestamp":1746001432000},"page":"e19313","source":"Crossref","is-referenced-by-count":1,"title":["Inhibitory effect of carvedilol on bedaquiline metabolism <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.7717","volume":"13","author":[{"given":"Qingqing","family":"Li","sequence":"first","affiliation":[{"name":"Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanshu","family":"Li","sequence":"additional","affiliation":[{"name":"Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hangjuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cixia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"issue":"4","key":"10.7717\/peerj.19313\/ref-1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.22f14584","article-title":"The practical importance of half-life in psychopharmacology","volume":"83","author":"Andrade","year":"2022","journal-title":"The Journal of Clinical Psychiatry"},{"issue":"5707","key":"10.7717\/peerj.19313\/ref-2","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1126\/science.1106753","article-title":"A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis","volume":"307","author":"Andries","year":"2005","journal-title":"Science"},{"issue":"12","key":"10.7717\/peerj.19313\/ref-3","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1055\/s-0031-1299835","article-title":"Drug-drug interactions of beta-adrenoceptor blockers","volume":"53","author":"Brodde","year":"2003","journal-title":"Arzneimittelforschung"},{"issue":"22","key":"10.7717\/peerj.19313\/ref-4","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.2146\/ajhp130199","article-title":"A review of tuberculosis: focus on bedaquiline","volume":"70","author":"Chan","year":"2013","journal-title":"American Journal of Health-System Pharmacy"},{"issue":"8","key":"10.7717\/peerj.19313\/ref-5","doi-asserted-by":"publisher","first-page":"e28519","DOI":"10.7759\/cureus.28519","article-title":"Bedaquiline: a novel diarylquinoline for multidrug-resistant pulmonary tuberculosis","volume":"14","author":"Deshkar","year":"2022","journal-title":"Cureus"},{"issue":"7","key":"10.7717\/peerj.19313\/ref-6","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1016\/S0735-1097(99)00134-5","article-title":"Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. 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