Internal medicine

CYP2E1

Dextromethorphan

Diabetes mellitus

CYP1A2

CYP3A

Endocrinology

CYP2C19

Tolbutamide

Chlorzoxazone

Type 2 diabetes

CYP2B6

Cytochrome P450

Metabolism

CYP2D6

CYP2C9

Medicine

Pharmacology

Clinical Pharmacology & Therapeutics

We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major cytochrome P450 ( CYP 450) activities. These activities were assessed in 38 T2D and 35 non‐T2D subjects after a single oral administration of a cocktail of probe drugs: 100 mg caffeine ( CYP 1A2), 100 mg bupropion ( CYP 2B6), 250 mg tolbutamide ( CYP 2C9), 20 mg omeprazole ( CYP 2C19), 30 mg dextromethorphan ( CYP 2D6), 2 mg midazolam ( CYP 3As), and 250 mg chlorzoxazone (alone; CYP 2E1). Mean metabolic activity for CYP 2C19, CYP 2B6, and CYP 3A was decreased in subjects with T2D by about 46%, 45%, and 38% ( P &lt; 0.01), respectively. CYP 1A2 and CYP 2C9 activities seemed slightly increased in subjects with diabetes, and no difference was observed for CYP 2D6 or CYP 2E1 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 CYP 450 activities in an isoform‐specific manner.

Modulation of <scp>CYP</scp>450 Activities in Patients With Type 2 Diabetes

Modulation of CYP450 Activities in Patients With Type 2 Diabetes