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

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.

Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats.

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 h 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.

[Hypoglycemic effects of bis(maltolato)oxovanadium administered by different routes upon diabetic rats].

OBJECTIVE: To study the hypoglycemic effects of bis(maltolato) oxovanadium (IV) (BMOV) after administration on diabetic rats by different routines, and its possible mechanisms. METHODS: Diabetic rats were created by intraperitoneal administration of Alloxan. BMOV was administered by single intraperitoneal injection, oral gavage, subcutaneous injection, bolus intravenous injection, or slow bolus intravenous injection(7-8 min). Plasma glucose levels were determined with blood glucose assay kits using the glucose oxidase method, while the plasma insulin concentrations were monitored by the insulin assay kits using Radioimmunoasssay (RIA) method. RESULTS: Plasma glucose levels were significantly decreased after administration of BMOV by all routes except intravenous injection. Food and fluid intake by the diabetic rats were also reduced. There was no significant increase in plasma insulin concentration. CONCLUSION: BMOV administered by oral gavage, subcutaneous injection and intraperitoneal injection has obvious effect of decreasing plasma glucose levels on diabetic rats, and the hypoglycemic effect of BMOV was not achieved by increasing the plasma insulin concentration.