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学科主题: 药学
题名:
Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats
作者: Zhang, SQ; Zhong, XY; Lu, WL; Zheng, L; Zhang, X; Sun, F; Fu, GY; Zhang, Q
关键词: vanadyl acetylacetonate ; pharmacodynamics ; pharmacokinetics ; tissue distribution
刊名: JOURNAL OF INORGANIC BIOCHEMISTRY
发表日期: 2005-05-01
DOI: 10.1016/j.jinorgbio.2005.01.015
卷: 99, 期:5, 页:1064-1075
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Chemistry, Inorganic & Nuclear
研究领域[WOS]: Biochemistry & Molecular Biology ; Chemistry
关键词[WOS]: BLOOD-GLUCOSE ; SULFATE ; COMPLEXES ; METABOLISM ; ABSORPTION ; LIGANDS
英文摘要:

The objectives of this study were to evaluate the pharmacodynamics and pharmacokinetics of vanadyl acetylacetonate (VAC) in rats. Pharmacodynamic study was carried out using non-diabetic and diabetic rats by subcutaneous (s.c.) and intragastric (i.g.) administrations at single dose or multiple doses. Pharmacokinetic study was performed using non-diabetic rats. Results showed that VAC resulted in a significant decrease of plasma glucose levels in diabetic rats in all dosing levels, and nearly restored hyperglycemic values to normal values after s.c. injection at a single dose of 2, 4, and 8 mg vanadium (V)/kg, or after i.g. administration at multiple doses of 3 and 6 mg V/kg once daily for seven consecutive days, respectively. The VAC could be rapidly absorbed and T-max values ranged from 0.9 +/- 0.3 h for s.c. injection to 3.0 +/- 0.9 h for i.g. administration. The average absolute bioavailabilities for i.g. administrations at a single dose of 3, 6, and 10 mg V/kg were 34.7%, 28.1%, and 22.8%, respectively. After i.g. administration at a single dose of 10 mg V/kg, the average elimination half-lives obtained from non-diabetic rats were very long ranging from 144.7 +/- 8.7 h in plasma to 657.3 +/- 34.8 It in femur tissue. In conclusion, VAC widely distributed in various tissues and accumulated more in the femur tissue. The time to reach maximal vanadium level after s.c. injection or i.g. administration was not coincident with the time to reach maximal hypoglycemic effect. The accumulated vanadium in bone, kidney or other tissues may gradually release and exert a longer action. In present dosing levels and administration routes, VAC was effective for lowering plasma glucose levels in diabetic rats and could reverse the higher triglyceride and cholesterol levels to the normal ranges. VAC did not influence the insulin levels in plasma and not cause obvious toxic signs like diarrhea. (c) 2005 Elsevier Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000228879200011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60478
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Ctr Hlth Sci, Dept Pharmaceut, Beijing 100083, Peoples R China
2.Affiliated Hosp, Acad Mil Med Sci, Beijing 100039, Peoples R China

Recommended Citation:
Zhang, SQ,Zhong, XY,Lu, WL,et al. Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats[J]. JOURNAL OF INORGANIC BIOCHEMISTRY,2005,99(5):1064-1075.
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