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.
Zhang
Shuang-Qing
SQ
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China. zhangshq@hotmail.com
Zhong
Xu-Ying
XY
Chen
Guo-Hua
GH
Lu
Wan-Liang
WL
Zhang
Qiang
Q
D000284:Administration, Oral; D000496:Alloxan; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000378:metabolism; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007668:Kidney / Q000378:metabolism; D008297:Male; D011753:Pyrones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014638:Vanadates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011753:Pyrones; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D000496:Alloxan