biostudies-literatureUnknown16Wang SY<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 IC₅₀ values of 14.01 ± 2.82 μM in rat liver microsomes and 52.40 ± 4.63 μM iFrontiers in pharmacology1643618https://www.ebi.ac.uk/biostudies/studies/S-EPMC12460146biostudies-literatureImpact of metabolic enzyme activity variability on dabrafenib disposition.PMC12460146Wang SYChen QChen JZhang XDChen LGChen ZXDai LSYuan JfalseImpact of metabolic enzyme activity variability on dabrafenib disposition.<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 IC₅₀ values of 14.01 ± 2.82 μM in rat liver microsomes and 52.40 ± 4.63 μM i2025-01-01T00:00:00Z20252026-06-03T22:44:45.771Z2026-05-31T03:06:31.968ZS-EPMC124601464101998410.3389/fphar.2025.1643618