{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16"],"submitter":["Wang SY"],"pubmed_abstract":["<h4>Introduction</h4>The systemic exposure of dabrafenib correlates with its adverse drug reactions. A thorough understanding of its pharmacokinetic profile is crucial for precise clinical application.<h4>Methods</h4>An optimized liver microsomal incubation system was established to screen for inhibitors of dabrafenib metabolism. Recombinant human CYP3A4 microsomes were prepared using a baculovirus-insect cell expression system. Analytes were quantified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo relevance of the inhibitory effects was further validated in Sprague-Dawley rats.<h4>Results</h4>Loratadine was identified as the most potent inhibitor, with IC<sub>50</sub> values of 14.01 ± 2.82 μM in rat liver microsomes and 52.40 ± 4.63 μM i"],"journal":["Frontiers in pharmacology"],"pagination":["1643618"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12460146"],"repository":["biostudies-literature"],"pubmed_title":["Impact of metabolic enzyme activity variability on dabrafenib disposition."],"pmcid":["PMC12460146"],"pubmed_authors":["Wang SY","Chen Q","Chen J","Zhang XD","Chen LG","Chen ZX","Dai LS","Yuan J"],"additional_accession":[]},"is_claimable":false,"name":"Impact of metabolic enzyme activity variability on dabrafenib disposition.","description":"<h4>Introduction</h4>The systemic exposure of dabrafenib correlates with its adverse drug reactions. A thorough understanding of its pharmacokinetic profile is crucial for precise clinical application.<h4>Methods</h4>An optimized liver microsomal incubation system was established to screen for inhibitors of dabrafenib metabolism. Recombinant human CYP3A4 microsomes were prepared using a baculovirus-insect cell expression system. Analytes were quantified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo relevance of the inhibitory effects was further validated in Sprague-Dawley rats.<h4>Results</h4>Loratadine was identified as the most potent inhibitor, with IC<sub>50</sub> values of 14.01 ± 2.82 μM in rat liver microsomes and 52.40 ± 4.63 μM i","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2026-06-03T22:44:45.771Z","creation":"2026-05-31T03:06:31.968Z"},"accession":"S-EPMC12460146","cross_references":{"pubmed":["41019984"],"doi":["10.3389/fphar.2025.1643618"]}}