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Abstract Title:

Enhanced oral bioavailability of docetaxel in rats combined with myricetin: In situ and in vivo evidences.

Abstract Source:

Eur J Pharm Sci. 2017 Apr 1 ;101:71-79. Epub 2017 Feb 7. PMID: 28185989

Abstract Author(s):

Tianyun Hao, Yunni Ling, Meijuan Wu, Yajing Shen, Yu Gao, Shujun Liang, Yuan Gao, Shuai Qian

Article Affiliation:

Tianyun Hao

Abstract:

The purpose of this study was to investigate the effect of myricetin on the pharmacokinetics of docetaxel in rats. In comparison to oral docetaxel alone (40mg/kg), the bioavailability of docetaxel could be significantly enhanced by 1.6-2.4-fold via oral co-administration with various flavonoids (apigenin, naringenin, baicalein, quercetin and myricetin) at a dosage of 10mg/kg, and myricetin showed the highest bioavailability improvement. Further pharmacokinetic studies demonstrated that the presence of myricetin (5-20mg/kg) enhanced both Cmax and AUC of docetaxel with the highest Cmax (162ng/mL, 2.3-fold) and relative bioavailability (244%) achieved at 10mg/kg of myricetin, while t1/2 was not influenced. In order to explore the reasons for such bioavailability enhancement of docetaxel, rat in situ single-pass intestinal perfusion model and intravenous docetaxel co-administrated with oral myricetin were carried out. After combining with myricetin, the permeability coefficient (Pblood) of docetaxel based on its appearance in mesenteric blood was significantly increased up to 3.5-fold in comparison to that of docetaxel alone. Different from oral docetaxel, the intravenous pharmacokinetics of docetaxel was not affected by co-administration of myricetin, indicating the limited effect of myricetin on the elimination of docetaxel. The above findings suggested that the oral bioavailability enhancement of docetaxel via co-administration with myricetin might be mainly attributed to the enhanced absorption in gastrointestinal tract rather than modulating the elimination of docetaxel.

Study Type : Animal Study

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Sayer Ji
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