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Effect of Aqueous Extract of Azadirachta indica Leaves on Pharmacokinetics and Pharmacodynamics of Glipizide.

Drug Metabolism Letters 2018 November 6
The intake of complementary and alternative medicines leads to various drug interactions, which may affect pharmacodynamics or pharmacokinetics. This study was conducted to determine the interaction of glipizide (GZ) with an aqueous extract of Azadirachta indica (AZI) leaves. The pharmacokinetics and pharmacodynamics were evaluated through the oral glucose tolerance test, high Fat diet (HFD) and streptozotocin-induced diabetes in Wistar rats. In vitro CYP3A Activity of AZI at 50µg and 100 µg was assessed using liver microsomes. Two doses of the AZI leaf extract (250 and 500 mg/kg) were administered alone or in combination with GZ (5 mg/kg) and serum glucose, AST, ALT, and ALP levels were estimated. In the glucose tolerance test, AZI and GZ showed a hypoglycemic effect. However, the hypoglycemic effect was lower when AZI was administered in combination with GZ compared with GZ alone. AZI at 100 µg has shown significant potentiation of CYP3A activity. AZI (500 mg/kg) pretreatment significantly decreased AUC and increased Tmax to 8 h. This indicates that the pharmacokinetics of GZ was altered by AZI and also suggesting that absorption of GZ was decreased may be due to P-glycoprotein induction. In conclusion, AZI can decrease the bioavailability of GZ, and hence, it should be cautiously used.

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