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Problem statement: Quercetin-a common bioflavonoid, is present &#13; in herbal preparations consumed by diabetic patients along with routine anti-diabetic &#13; agents. We recently showed that quercetin increases the bioavailability of pioglitazone &#13; in non-diabetic rats. Thus, present study investigated whether this pharmacokinetic &#13; interaction is also evident in diabetic animals, especially because diabetic subjects &#13; have altered gastrointestinal (GI) function and CYP3A activity. Approach: &#13; The study was carried out in alloxan-induced (40 mg kg-1, i.v.) diabetic &#13; rats. After 2 weeks of diabetes induction, rats were treated for 2 weeks with &#13; quercetin (10 mg kg-1, p.o.) or vehicle (5% methyl cellulose, 10 mL kg-1). At &#13; the end of 4 weeks, these rats were used to investigate: (1) GI function in terms &#13; of gastric emptying and intestinal transit of semisolid barium sulphate meal; &#13; (2) CYP3A activity in liver and intestinal microsomes by erythromycin N-demethylase &#13; assay; (3) Plasma levels of orally and intravenously administered pioglitazone &#13; (10 mg kg-1, p.o.; 5 mg kg-1, i.v.). Results: The results revealed &#13; that diabetic rats exhibited: (1) Delayed gastric emptying and intestinal transit; &#13; (2) Decreased CYP3A activity and (3) A significant increase in the oral and intravenous &#13; AUC0-&#8734; of pioglitazone as compared to non-diabetic rats. Quercetin treatment prevented &#13; the diabetes-induced GI dysfunction, whereas diabetes-induced decrease in CYP3A &#13; activity and increased bioavailability of pioglitazone remained unaffected. &#13; Conclusion: The results suggested that quercetin attenuated GI dysfunction &#13; but did not affect the bioavailability of pioglitazone in diabetic rats contrary &#13; to the increase reported in non-diabetic rats. However, the safety of co-joint &#13; use of quercetin containing herbs and pioglitazone in clinical practice requires &#13; further pharmacokinetic substantiation

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