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Comparative Oral and Intravenous Pharmacokinetics of Phlorizin in Type 2 diabetes and Normal Rats Base on Phase II Metabolism

Abstract

Phlorizin (PHZ) is a kind of dihydrochalcone and widely found in Rosaceae such as apple, which is the first compound discovered as sodium-glucose cotransporter (SGLT) inhibitor, and has been confirmed to improve the symptoms of diabetes and diabetic complications effectively. As it is known that PHZ is metabolized into flavonoid glycosides through wide phase I and II metabolism in digestive tract, which results in poor bioavailability as well as seriously reduction of nutritional value. Based on the previous report, this study was attempted to investigate the pharmacokinetics and contribution degree of phase II metabolism after oral and intravenous administration of PHZ in rats. Furthermore, the pharmacokinetics, bioavailability and metabolism of PHZ in type 2 diabetes (T2D) rats and normal rats were respectively measured since PHZ plays a key role in treatment of diabetes mellitus. Sulfatase and β-glucuronidase were used for phase II metabolism study. Results showed that contribution ratio of phase II metabolism of PHZ ranged from 41.9% to 69.0% after intravenous injection. The AUC0-t and Cmax of PHZ in T2D rats were significantly increased than that of normal rats, which was accompanied with significant decrease in T1/2 in T2D rats compared with that of normal rats. Overactive deglycosylation of PHZ resulted in production of numerous PHT after oral administration, and almost all the PHT was further involved in phase II metabolism and transformed into conjugates with glycose after both oral and intravenous administration of PHZ in rats. Moreover, it was found that the bioavailability of PHZ in T2D rats were about 5%, which was significantly increased than that in normal rats (0% vs 5%, respectively). In conclusion, the pharmacokinetic behavior of PHZ was significantly changed in T2D rats after both orally and intravenously administration of PHZ, and results showed the bioavailability of PHZ was significantly increased in T2D rats compared with that in normal rats. Besides, the phase II metabolites of PHT were the major existence form in blood after oral and intravenous administration. This provides a reference for the later development of PHZ into drug or functional food for the treatment of diabetes.

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Publication details

The article was received on 14 Nov 2018, accepted on 07 Feb 2019 and first published on 08 Feb 2019


Article type: Paper
DOI: 10.1039/C8FO02242A
Citation: Food Funct., 2019, Accepted Manuscript

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    Comparative Oral and Intravenous Pharmacokinetics of Phlorizin in Type 2 diabetes and Normal Rats Base on Phase II Metabolism

    Z. Wang, Z. Gao, A. Wang, L. Jia, X. Zhang, M. Fang, K. Yi, Q. Li and H. Hu, Food Funct., 2019, Accepted Manuscript , DOI: 10.1039/C8FO02242A

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