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Evaluation of Important Human Cyp450 Isoforms and P-Glycoprotein Phenotype Changes and Genotype in Type 2 Diabetic Patients, Before and After Intensifying Treatment Regimen Using Geneva Cocktail Publisher Pubmed



Neyshaburinezhad N1 ; Shirzad N2 ; Rouini M1 ; Namazi S3 ; Khoshayand M4 ; Esteghamati A2 ; Nakhjavani M2 ; Ghasim H1 ; Gloor Y5 ; Daali Y5 ; Ardakani YH1
Authors
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Authors Affiliations
  1. 1. Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland

Source: Basic and Clinical Pharmacology and Toxicology Published:2023


Abstract

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL-1β and IL-6), genotypes, diabetes and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner. © 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.
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