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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 treatment, by using Geneva cocktail
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  • Navid Neyshaburinezhad,
  • Nooshin Shirzad,
  • Mohammadreza Rouini,
  • Soha Namazi,
  • Mohammadreza Khoshayand,
  • Alireza Esteghamati,
  • Manooshehr Nakhjavani,
  • Hengameh Ghasim,
  • Youssef Daali,
  • Yalda H. Ardakani
Navid Neyshaburinezhad
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Nooshin Shirzad
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Mohammadreza Rouini
Tehran University of Medical Sciences School of Pharmacy
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Soha Namazi
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Mohammadreza Khoshayand
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Alireza Esteghamati
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Manooshehr Nakhjavani
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Hengameh Ghasim
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Youssef Daali
University of Geneva Faculty of Medicine
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Yalda H. Ardakani
Tehran University of Medical Sciences School of Pharmacy

Corresponding Author:[email protected]

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The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 isoforms and P-glycoprotein (P-gp) transporter activities before and 3 months after intensifying treatment regimen of 40 patients. Results have been compared with 21 non-T2D healthy participants (control group). CYPs and P-gp activities were assessed after administration of Geneva cocktail. Mean metabolic ratios (MR) for CYP2B6 (1.81±0.93 vs. 2.68±0.87), CYP2C19 (0.420 ± 0.360 vs. 0.687 ± 0.558), and CYP3A4/5 (0.487 ± 0.226 vs. 0.633 ± 0.254) significantly decreased in T2D subjects compared to control group (p<0.05). CYP2C9 (0.089±0.037 vs. 0.069±0.017) activities slightly increased in diabetic subjects and no difference was observed for CYP1A2 (0.154±0.085 vs. 0.136±0.065), CYP2D6 (1.17 ± 0.56 vs. 1.24 ± 0.83) and P-gp activities in comparison with control group. Three months after intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) have shown a significant improvement and were not statistically different compared to 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 our analyses. Our results indicate that low chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform specific manner.
02 Dec 2022Submitted to Basic & Clinical Pharmacology & Toxicology
05 Dec 2022Submission Checks Completed
05 Dec 2022Assigned to Editor
05 Dec 2022Review(s) Completed, Editorial Evaluation Pending
05 Dec 2022Reviewer(s) Assigned
27 Dec 2022Editorial Decision: Revise Major
02 Jan 20231st Revision Received
03 Jan 2023Assigned to Editor
03 Jan 2023Review(s) Completed, Editorial Evaluation Pending
03 Jan 2023Submission Checks Completed
03 Jan 2023Reviewer(s) Assigned
24 Jan 2023Editorial Decision: Revise Major
25 Jan 20232nd Revision Received
26 Jan 2023Submission Checks Completed
26 Jan 2023Assigned to Editor
26 Jan 2023Review(s) Completed, Editorial Evaluation Pending
27 Jan 2023Editorial Decision: Accept