Pharmacokinetic studies of 1α, 24(R)-(OH)₂D₃ (TV-02) (1) Plasma level, distribution metabolism and excretion after a single subcutaneous administration to rats.

Abstract

³H-TV-02 was administered subcutaneously (0.4μg/kg), in order to investigate the excretion, plasma profiles and distribution.
1. Urinary and fecal excretion of radioactivity within 10 days after administration, was about 18% and 76% of the dose, respectively.
2. Approximately 75% of total administred radioactivity was excreted into bile, in which calcitroic acid and a little of unchanged TV-02 were detected.
3. The plasma levels of the radioactivity in lipid extracts and unchanged TV-02 reached the maximum at 2hr after administration, then underwent two-phase elimination (T_1/2(α)=2.3hr, T_1/2(β)=434.2hr for the radioactivity in lipid extracts and T_1/2(α)=2.2hr, T_1/2(β)=22.3hr for unchanged TV-02). Only 1α, 24(R)25-(OH)₃D₃ was detected as the metabolite in plasma.
4. The concentration of radioactivity (in lipid extracts) in the site of injection decreased rapidly to the same values as that in plasma at 24hr after injection.
The level of radioactivity in liver, small intestine, and kidney were virtually close to plasma level, and those in other tissues were much lower.