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Modulation of CYP 450 Activities in Patients With Type 2 Diabetes
Author(s) -
Gravel Sophie,
Chiasson JeanLouis,
Turgeon Jacques,
Grangeon Alexia,
Michaud Veronique
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1496
Subject(s) - tolbutamide , cyp2b6 , cyp2c19 , cyp1a2 , chlorzoxazone , type 2 diabetes , pharmacology , cyp3a , cyp2d6 , cyp2c9 , medicine , diabetes mellitus , cyp2e1 , dextromethorphan , cytochrome p450 , endocrinology , metabolism
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 < 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.