TY  - JOUR
AU  - Umathe, Sudhir Niranjan 
AU  - Dixit, Pankaj Vinod 
AU  - Vaghasiya, Jignesh Manubhai 
AU  - Jain, Nishant Sudhir 
PY  - 2009
TI  - Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats
JF  - American Journal of Infectious Diseases
VL  - 5
IS  - 2
DO  - 10.3844/ajidsp.2009.118.125
UR  - https://thescipub.com/abstract/ajidsp.2009.118.125
AB  - 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.