Biodistribution and pharmacokinetics of vanadium following intraperitoneal administration of vanadocene dichloride to mice

The biodistribution and pharmacokinetics of vanadium following i.p. administration of vanadocene dichloride (VDC), a representative of a new class of organometallic anticancer agents, is reported for Strain A mice. A convenient flameless atomic absorption spectroscopic assay is described and is used to determine kinetic profiles for vanadium in blood, kidney, liver, small intestine and brain tissue for times up to 24 h after administration. For a VDC dose of 80 mg/kg, vanadium concentration decreases rapidly from both the blood and small intestine, and the data can be fit to a phenomenological exponential function (blood: t1/2 = 118 +/- 43 min; small intestine: t1/2(alpha) = 18.10 +/- 0.14 min, t1/2(beta) = 341 +/- 45 min). In contrast, vanadium accumulates in both the kidney and liver up to a maximal concentration (1.12 +/- 0.06 mM and 0.56 +/- 0.06 mM after 12 and 8 h, respectively), and is then excreted with estimated half-lives of 7.9 +/- 0.7 and 12.1 +/- 0.1 h, respectively. No detectable levels of vanadium are found in the brain tissue over the temporal course of the experiment. These results are compared to previous mammalian studies with cis-dichlorodiammineplatinum(II) (CDDP) and related 'second generation' platinum derivatives; there are both qualitative similarities between the vanadium and platinum systems as well as important quantitative differences.