TITLE

Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats

AUTHOR(S)
Umathe, Sudhir Niranjan; Dixit, Pankaj Vinod; Vaghasiya, Jignesh Manubhai; Jain, Nishant Sudhir
PUB. DATE
April 2009
SOURCE
American Journal of Infectious Diseases;2009, Vol. 5 Issue 2, p125
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 nondiabetic rats. However, the safety of co-joint use of quercetin containing herbs and pioglitazone in clinical practice requires further pharmacokinetic substantiation.
ACCESSION #
43899420

 

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