Coordination chemistry may explain pharmacokinetics and clinical response of vanadyl sulfate in type 2 diabetic patients

摘要: Vanadium, abbreviated V, is an early transition metal that readily forms coordination complexes with a variety of biological products such as proteins, metabolites, membranes and other structures. The formation stabilizes ions, which in turn impacts the biodistribution metal. To understand V oxidation state iv form vanadyl sulfate (25, 50, 100 mg daily) was given orally for 6 weeks to 16 persons type 2 diabetes. Elemental determined using Graphite Furnas Atomic Absorption Spectrometry against known concentrations serum, blood or urine. Peak serum levels were 15.4 ± 6.5, 81.7 40 319 268 ng ml(-1) respectively, mean peak positively correlated dose administered (r = 0.992, p 0.079), although large inter-individual variability found. Total concentration distribution fit one compartment open model first order rate constant excretion half times 4.7 1.6 days 4.6 2.5 50 groups respectively. At steady state, 24 hour urinary output 0.18 0.24 0.97 0.84 consistent absorption 1 percent less dose. 0.971, < 0.0005). ratio patients receiving 1.7 0.45. Regression analysis showed glycohemoglobin negative predictor natural log(ln) (R(2) 0.40, 0.009) positive euglycemic-hyperinsulinemic clamp results at high insulin values 0.39, 0.010). Insulin sensitivity measured by not significantly ln V. Globulin taken together predictors fasting glucose 0.49, 0.013). Although accumulation dose-dependent, no correlation between total insulin-like response found this attempt correlate anti-diabetic activity This study suggests pools than are likely related effect These results, obtained diabetic patients, document need consideration chemistry metabolites proteins vanadium complexes.