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Scientific article
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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

Published inBasic & clinical pharmacology & toxicology, vol. 132, no. 6, p. 487-499
Publication date2023-06
First online date2023-03-21
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.

eng
Keywords
  • CYP450 phenotype and genotype
  • Inflammation
  • Personalized medicine
  • Phenoconversion
  • Type 2 diabetes
  • Humans
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Cytochrome P-450 CYP2C9 / genetics
  • Cytochrome P-450 CYP2C9 / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Phenotype
  • Genotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • ATP Binding Cassette Transporter, Subfamily B / genetics
Citation (ISO format)
NEYSHABURINEZHAD, Navid et al. 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. In: Basic & clinical pharmacology & toxicology, 2023, vol. 132, n° 6, p. 487–499. doi: 10.1111/bcpt.13840
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Article (Published version)
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Identifiers
ISSN of the journal1742-7835
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Creation02/06/2024 11:11:58 AM
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