Kinetic analysis and comparison of uptake, distribution, and excretion of⁴⁸V-labeled compounds in rats

Abstract

Setyawati, I. A., K. H. Thompson, V. G. Yuen, Y. Sun, M. Battell, D. M. Lyster, C. Vo, T. J. Ruth, S. Zeisler, J. H. McNeill, and C. Orvig. Kinetic analysis and comparison of uptake, distribution, and excretion of 48 V-labeled compounds in rats. J. Appl. Physiol. 84(2): 569–575, 1998.—Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(IV) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using 48 V as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of 48 V-BMOV compared with 48 VS. The highest 48 V concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested 48 V was eliminated unabsorbed by fecal excretion. On average, 48 V concentrations in bone, kidney, and liver 24 h after oral administration of 48 V-BMOV were two to three times higher than those of 48 VS, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.