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However, changes in drug\u2010induced CYP expression under pathological conditions have not been elucidated in detail. Here, we investigated the effects of hepatic inflammation and injury on phenobarbital\u2010induced expression of CYP isoforms in mice. Phenobarbital was administered once as a CYP inducer in the carbon tetrachloride\u2010induced hepatitis model mice. The mRNA expression levels of Cyp3a11 and Cyp2b10 in the liver and small intestine were measured using reverse transcription polymerase chain reaction. The enzymatic activity of CYP3A in liver S9 was evaluated using midazolam as the substrate. Phenobarbital increased the mRNA expression of Cyp3a11 and Cyp2b10 in the liver of healthy mice, but not in the small intestine. Increased mRNA expression of hepatic Cyp3a11 and Cyp2b10 by phenobarbital was significantly suppressed in the hepatitis model mice. Hepatitis also suppressed the increased CYP3A enzymatic activity induced by phenobarbital in liver S9, consistent with the results of Cyp3a11 mRNA expression. These results suggest that the inducibility of CYP by phenobarbital may vary in patients with hepatitis, indicating that pharmacokinetic drug\u2013drug interactions can be altered under certain pathological conditions.<\/jats:p>","DOI":"10.1002\/bdd.2356","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T04:40:06Z","timestamp":1681101606000},"page":"351-357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Attenuation of phenobarbital\u2010induced cytochrome P450 expression in carbon tetrachloride\u2010induced hepatitis in mice models"],"prefix":"10.1002","volume":"44","author":[{"given":"Chieri","family":"Fujino","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences Ritsumeikan University  Kusatsu\u2010shi Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiki","family":"Kuzu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Ritsumeikan University  Kusatsu\u2010shi Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukine","family":"Kubo","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Ritsumeikan University  Kusatsu\u2010shi Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurumi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Ritsumeikan University  Kusatsu\u2010shi Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Ueshima","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Ritsumeikan University  Kusatsu\u2010shi Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7789-8803","authenticated-orcid":false,"given":"Toshiya","family":"Katsura","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Ritsumeikan University  Kusatsu\u2010shi Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102613.2011.00803.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1093"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010018\u20101136\u20102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114433"},{"key":"e_1_2_9_6_1","first-page":"760","article-title":"Human hepatocyte growth factor down\u2010regulates the expression of cytochrome P450 isozymes in human hepatocytes in primary culture","volume":"284","author":"Donato M. 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