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双(麦芽醇)氧钒在非糖尿病和糖尿病大鼠中的抗糖尿病作用及药代动力学特征。

The anti-diabetic effects and pharmacokinetic profiles of bis(maltolato)oxovanadium in non-diabetic and diabetic rats.

作者信息

Zhang Shuang-Qing, Zhong Xu-Ying, Chen Guo-Hua, Lu Wan-Liang, Zhang Qiang

机构信息

School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.

出版信息

J Pharm Pharmacol. 2008 Jan;60(1):99-105. doi: 10.1211/jpp.60.1.0013.

Abstract

The purpose of this study was to evaluate the anti-diabetic effects and pharmacokinetics of bis(maltolato)oxovanadium (BMOV) in rats. The anti-diabetic study was carried out in non-diabetic and diabetic rats by single-dose subcutaneous and intragastric administration. Pharmacokinetic investigation was performed using non-diabetic rats. Results showed that BMOV significantly decreased plasma glucose levels in diabetic rats at all given doses, and restored hyperglycaemic values to normal values after subcutaneous injections at doses of 4 and 8 mg vanadium (V)/kg or after intragastric administration at doses of 14 and 28 mgV/kg, respectively, but did not affect the plasma glucose level in non-diabetic rats. BMOV could be rapidly absorbed, slowly eliminated from plasma, widely distributed in various tissues and accumulated to a greater extent in the femur tissue. The average absolute bioavailability for intragastric administration at a single dose of 3, 6 and 12 mgV/kg was 28.1%, 33.7% and 21.4%, respectively. The presence of the peak vanadium level in the plasma was not coincident with that of the maximum effect of lowering plasma glucose levels. In conclusion, at the present dosing levels and administration routes, BMOV was effective in lowering plasma glucose levels in diabetic rats. BMOV has a promising outlook as an oral glucose-lowering drug.

摘要

本研究旨在评估双(麦芽醇根)氧钒(BMOV)对大鼠的抗糖尿病作用及药代动力学。通过单剂量皮下和胃内给药,在非糖尿病和糖尿病大鼠中进行抗糖尿病研究。使用非糖尿病大鼠进行药代动力学研究。结果表明,在所有给药剂量下,BMOV均能显著降低糖尿病大鼠的血糖水平,在皮下注射4和8 mg钒(V)/kg剂量或胃内给药14和28 mgV/kg剂量后,分别能将高血糖值恢复至正常水平,但对非糖尿病大鼠的血糖水平无影响。BMOV可被快速吸收,从血浆中缓慢消除,广泛分布于各种组织中,并在股骨组织中积累程度更高。单剂量3、6和12 mgV/kg胃内给药的平均绝对生物利用度分别为28.1%、33.7%和21.4%。血浆中钒水平的峰值与降低血糖水平的最大效应并不一致。总之,在目前的给药水平和给药途径下,BMOV对降低糖尿病大鼠的血糖水平有效。BMOV作为一种口服降糖药物具有广阔的前景。

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