Abstract
We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major cytochrome P450 (CYP450) activities. These activities were assessed in 38 T2D and 35 non-T2D subjects after a single oral administration of a cocktail of probe drugs: 100mg caffeine (CYP1A2), 100mg bupropion (CYP2B6), 250mg tolbutamide (CYP2C9), 20mg omeprazole (CYP2C19), 30mg dextromethorphan (CYP2D6), 2mg midazolam (CYP3As), and 250mg chlorzoxazone (alone; CYP2E1). Mean metabolic activity for CYP2C19, CYP2B6, and CYP3A was decreased in subjects with T2D by about 46%, 45%, and 38% (P<0.01), respectively. CYP1A2 and CYP2C9 activities seemed slightly increased in subjects with diabetes, and no difference was observed for CYP2D6 or CYP2E1 activities. Several covariables, such as inflammatory markers (interleukin (IL)-1ß, IL-6, gamma interferon, and tumor necrosis factor alpha), genotypes, and diabetes-related and demographic-related factors were considered in our analyses. Our results indicate that low chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.
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