Modulation of CYP450 Activities in Patients With Type 2 Diabetes.

Autor: Gravel S; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada., Chiasson JL; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada., Turgeon J; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada., Grangeon A; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada., Michaud V; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2019 Dec; Vol. 106 (6), pp. 1280-1289. Date of Electronic Publication: 2019 Jul 09.
DOI: 10.1002/cpt.1496
Abstrakt: 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: 100 mg caffeine (CYP1A2), 100 mg bupropion (CYP2B6), 250 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan (CYP2D6), 2 mg midazolam (CYP3As), and 250 mg 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.
(© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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