Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats
Sudhir Niranjan Umathe, Pankaj Vinod Dixit, Jignesh Manubhai Vaghasiya and Nishant Sudhir Jain
DOI : 10.3844/ajidsp.2009.118.125
American Journal of Infectious Diseases
Volume 5, Issue 2
Problem statement: Quercetin-a common bioflavonoid, is present in herbal preparations consumed by diabetic patients along with routine anti-diabetic agents. We recently showed that quercetin increases the bioavailability of pioglitazone in non-diabetic rats. Thus, present study investigated whether this pharmacokinetic interaction is also evident in diabetic animals, especially because diabetic subjects have altered gastrointestinal (GI) function and CYP3A activity. Approach: The study was carried out in alloxan-induced (40 mg kg-1, i.v.) diabetic rats. After 2 weeks of diabetes induction, rats were treated for 2 weeks with quercetin (10 mg kg-1, p.o.) or vehicle (5% methyl cellulose, 10 mL kg-1). At the end of 4 weeks, these rats were used to investigate: (1) GI function in terms of gastric emptying and intestinal transit of semisolid barium sulphate meal; (2) CYP3A activity in liver and intestinal microsomes by erythromycin N-demethylase assay; (3) Plasma levels of orally and intravenously administered pioglitazone (10 mg kg-1, p.o.; 5 mg kg-1, i.v.). Results: The results revealed that diabetic rats exhibited: (1) Delayed gastric emptying and intestinal transit; (2) Decreased CYP3A activity and (3) A significant increase in the oral and intravenous AUC0-∞ of pioglitazone as compared to non-diabetic rats. Quercetin treatment prevented the diabetes-induced GI dysfunction, whereas diabetes-induced decrease in CYP3A activity and increased bioavailability of pioglitazone remained unaffected. Conclusion: The results suggested that quercetin attenuated GI dysfunction but did not affect the bioavailability of pioglitazone in diabetic rats contrary to the increase reported in non-diabetic rats. However, the safety of co-joint use of quercetin containing herbs and pioglitazone in clinical practice requires further pharmacokinetic substantiation.
© 2009 Sudhir Niranjan Umathe, Pankaj Vinod Dixit, Jignesh Manubhai Vaghasiya and Nishant Sudhir Jain. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.