Organ distribution and pharmacokinetics of titanium after treatment with titanocene dichloride

The pharmacokinetics and organ distribution of titanium (Ti) were analyzed at various intervals up to 96 h after a single i.p. injection of a therapeutic dose of the antitumor agent titanocene dichloride (TDC, 60 mg/kg) by use of flameless atomic absorption spectroscopy in dried organ specimens. Highest organ concentrations were found in the liver and the intestine where 80-90 mg Ti/kg dry weight were accumulated at 24 and 48 h, corresponding to liver/blood and intestine/blood ratios of 8-9. However, at no time point after the TDC application, the Ti concentrations in brain tissue exceeded those of control animals. In solid tumors growing subcutaneously in mice, increasing amounts of Ti were found during the course of the experiment, reaching concentrations between 10 and 15 mg Ti/kg at 24 and 96 h after single i.p. application of TDC. These results confirm a typical pattern of organ distribution of Ti-containing metabolites of TDC, which clearly differs from that observed for vanadium after application of vanadocene dichloride or for platinum after treatment with cisplatin.