Evaluating the effect of type 2 diabetes mellitus on CYP450 enzymes and P-gp activities, before and after glycemic control: a protocol for a case-control pharmacokinetic study: Evaluation of metabolism in diabetes mellitus

Abstract Cytochrome P450s (CYP450) family is one of the most critical factors in the metabolism process. Hence, the present study aims to characterize the activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, and P-glycoprotein (P-gp) pump in patients with type 2 diabetes (T2DM). This characterization was performed before and after good glycemic control versus non-diabetic subjects following the administration of a substrate probe drug cocktail. This single-center clinical study proposes the characterization of T2DM impacts on major CYP450 drug-metabolizing enzyme and P-glycoprotein (P-gp) activities. The main propose of the present study is evaluating any alternation in major CYP450 enzymes and P-gp activities in patients with T2DM, before (A1C>7%) and after (A1C≤7%) good glycemic control along with comparing the activities versus non-diabetic subjects. The phenotypes will be assessed following the oral administration of a drug cocktail containing caffeine (CYP1A2), bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A4/5), and fexofenadine (P-gp) as probe substrates. Besides, the effect of some variables such as blood glucose levels and inflammation on the metabolism process will be examined. Furthermore, the influence of variables such as glycemia, genetic polymorphisms, and inflammation will be evaluated. The first patient has entered the study in Dec 2018.