Abstract：
:Herbal antidiabetic preparations are often used as an add-on therapy in diabetes and such herbal preparations often contains quercetin that can inhibit cytochrome P450 (CYP) 3A4. This enzyme is responsible for metabolizing pioglitazone, a commonly used antidiabetic agent. Hence, it was speculated that quercetin may influence the bioavailability of pioglitazone, which could be particularly crucial, as any increment in its plasma levels may raise safety concerns. Thus, we first established the inhibitory influence of quercetin (2, 10 and 20 mg/kg, p.o.) on CYP3A activity by an in vivo method of estimating levels of midazolam in female rats pretreated with dexamethasone. It was further confirmed in vitro using erythromycin-N-demethylase (EMD) assay. These studies indicated potent inhibition of CYP3A activity by quercetin (10 and 20 mg/kg, in vivo; 1 and 10 microM, in vitro). In another experiment, pioglitazone was administered orally (10 mg/kg) and intravenously (5mg/kg) to quercetin (10 mg/kg) pretreated female rats and its plasma levels were determined at various time points (0.5, 1, 2, 4, 8 and 24 h after oral administration; 0.083, 0.5, 1, 2, 8, 12 and 18 h after i.v. administration) by HPLC. Quercetin pretreatment increased AUC(0-infinity) of pioglitazone after oral administration by 75% and AUC(0-infinity) after intravenous administration by 25% suggesting decreased metabolism, which could be due to inhibition of CYP3A by quercetin. In conclusion, add-on preparations containing quercetin may increase the bioavailability of pioglitazone, and hence should be cautiously used.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Umathe SN,Dixit PV,Kumar V,Bansod KU,Wanjari MMdoi
10.1016/j.bcp.2008.01.010subject
Has Abstractpub_date
2008-04-15 00:00:00pages
1670-6issue
8eissn
0006-2952issn
1873-2968pii
S0006-2952(08)00062-2journal_volume
75pub_type
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