@article {10.3844/ajidsp.2009.118.125, article_type = {journal}, title = {Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats}, author = {Umathe, Sudhir Niranjan and Dixit, Pankaj Vinod and Vaghasiya, Jignesh Manubhai and Jain, Nishant Sudhir}, volume = {5}, number = {2}, year = {2009}, month = {Jun}, pages = {118-125}, doi = {10.3844/ajidsp.2009.118.125}, url = {https://thescipub.com/abstract/ajidsp.2009.118.125}, abstract = {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.}, journal = {American Journal of Infectious Diseases}, publisher = {Science Publications} }