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First published online August 1, 2015

Effects of Thymoquinone on the Pharmacokinetics and Pharmacodynamics of Glibenclamide in a Rat Model

Abstract

Glibenclamide and thymoquinone plasma concentrations were analysed using a sensitive RP-HPLC method, and non-compartmental model pharmacokinetic parameters were calculated. The maximum reduction in blood glucose level was observed 3 hours following glibenclamide administration, which reached 47.4% of baseline, whereas it was reduced by 53.0% to 56.2% when co-administrated with thymoquinone. Plasma concentration of glibenclamide was increased by 13.4% and 21.8% by the co-administration of thymoquinone as single and multiple doses, respectively (P<0.05). The AUC and T1/2 of glibenclamide were also increased respectively by 32.0% and 17.4% with a thymoquinone single dose, and by 52.5% and 92.8% after chronic treatment. Furthermore, diabetic rats treated with thymoquinone demonstrated a marked decrease in hepatic protein expressions of CYP3A2 and CYP2C11 enzymes that are responsible for the metabolism of glibenclamide. The current data suggest that thymoquinone exhibits a synergistic effect with glibenclamide on glucose level, which could be explained by reducing CYP450 activity at the protein level.

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Article first published online: August 1, 2015
Issue published: August 2015

Keywords

  1. Diabetes
  2. Glibenclamide
  3. Thymoquinone
  4. Pharmacokinetic
  5. Pharmacodynamic
  6. Interaction

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Authors

Affiliations

Ajaz Ahmad
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
Rao Muzaffar A. Khan
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
Khalid M. Alkharfy
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
Mohammad Raish
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
Fahad I. Al-Jenoobi
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
Abdullah M. Al-Mohizea
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

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