Opportunities for pharmacological modulation cytochrome P450 isoenzymes metabolizing sulfonylurea derivatives
Sulfonylureas are the leaders in the treatment of diabetes mellitus (DM) type 2. The most commonly prescribed preparation of the whole group of sulfonylureas are glibenclamide, gliclazide or glimepiride. Sulfonylureas eliminate from a body out by biotransformation involving cytochrome P-450 (CYP450): CYP2C9 and CYP2C19. Sulfonylureas, especially glibenclamide are able to deplete the reserves of metabolizing isoenzymes causing a threat of hypoglycemia. Among the other risk factors one should mention genetically deterministic low metabolic activity of CYP2C9 and CYP2C19. This type of patients have an increased risk of sulfonylurea-associated hypoglycemia. The article presents a project of the study protocol developed by a group of authors regarding the possibility of using hepatoprotectors for recovering the activity of CYP450 whether it’s reduction is acquired or genetically conditioned. The purpose of the study described in the protocol was to study the modulating influence of hepatoprotectors on the activity of CYP2C9 isoenzyme in reversible stages of nonalcoholic fatty liver disease in patients with type 2 diabetes and evaluate the efficacy and safety of these drugs in the mentioned group of patients. It describes the examples of diagnosing, differential diagnosis, diagnostic criteria stages of non-alcoholic fatty liver disease on the background of type 2 diabetes and metabolic syndrome. The study design includes the following: forming a group of patients studied, inclusion criteria, exclusion criteria, disregard criteria (removal) from the study, method of dividing patients into groups, test methods. Efficacy and safety criteria include the efficacy and safety assessment.