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

Abstract

Plasma profiles, tissue distribution and excretion of ³H-TV-02 ([1β-³H]-1 α, 24(R)-(OH)₂D₃) were investigated in rats after repeated subcutaneous adm inistration (7 or 2ltimes) at the dose of 0.4μg/kg/day.
The radioactivity in lipid extracts from plasma consisted of unchanged TV-02 and small amounts of 1, 24(R), 25-(OH)₃D₃ whose vitamin D₃-like activity was weaker than that of TV-02. The maximal plasma levels of radioactivity following administration of the 21st dose were about 1.5times higher after 7 th dose and nearly equal to a single dose.
The unchanged TV-02 was rapidly eliminatdd from the injection site, liver, small intestine and adipose tissue in which the levels of radioactivity were higher than in plasma after 21st administration.
Urinary and fecal excretion amounted to 10.8% and 87.6% of the total dose of radioactivity during and after 2ltimes repeated administration, respectively.