Evidence-based P-glycoprotein inhibition by green tea extract enhanced the oral bioavailability of atorvastatin: from animal and human experimental studies

Abstract

Background: The study aimed to explore the beneficial effects of green tea extract (GTE) on the permeability and absorption kinetics of atorvastatin in rats and healthy human volunteers. Methods: Wistar rats for both in situ and in vivo studies. In in situ Single pass intestinal perfusion study, three groups (n = 6), wherein Group 1 perfused with atorvastatin as control, Group 2 coperfused with verapamil, and Group 3 coperfused with GTE then the effective permeability of atorvastatin was determined. In in vivo study, three groups (n = 6), wherein Group 1 is treated with atorvastatin as control, Group 2 pre-treatment with verapamil for 7 days and Group 3 pretreatment with GTE for 7 days and on 8th day atorvastatin was repeated and subjected to pharmacokinetic study. These results were confirmed on 24 healthy human volunteers, the randomized crossover trial was carried with atorvastatin for 11 days to check the bioavailability of atorvastatin by pre-treatment with GTE. Blood samples collected between 0.5 and 24 h on day-1, following administration of atorvastatin. Blood sampling was repeated using similarly specified time intervals on day-11, after treating human volunteers with GTE capsule 400 mg for 10 days. Results: Effective permeability of atorvastatin has been increased by GTE in in situ studies. The clearance of atorvastatin was decreased by 17.5% (P < 0.001), and Cmaxwas increased many folds significantly in in vivo studies. A significant increase in serum concentrations of atorvastatin was observed from 1st h. Cmax, bioavailability were increased by 14.5% (P < 0.05), and 22.7% (P < 0.001), respectively, in human volunteers. Conclusion: Increased bioavailability of atorvastatin is due to the P-gp inhibition by GTE, leads to the reduced dose. Further anti-hyperlipidemic activity of the GTE enables the dyslipidemic patients to take this herbal product safely.