Pharmacokinetic studies of 1α, 24(R)-(OH)₂D₃(TV-02)(3):Absorption, distribution and excretion after a single or continuous transcutaneous application to rats

Abstract

The excretion, plasma profiles and tissue distribution of ³H-TV-02 ([1β-³H]-1α, 24(R)-(OH)₂D₃) were investigated in rats after a single and continuous (7days) transcutaneous application.
After a single application (0.4μg/100mg ointment/head), the respective recovery of radioactivity in urine and feces during 11days was 3.6 and 26.2% of the dose. Biliary excretion of radioactivity during 32hrs accounted for 32.5 % of the dose.
The plasma concentration of radioactivity in lipid extracts reached a maximum after 2hr and declined slowly during the application, while after the withdrowal of ointment the elimination was fast.
The level of radioactivity at the application site, practically originating from TV-02, corresponded to more than 6800pg/g tissue during the application. The distribution of radioactivity usually was significant in liver, small intestine and kidney being conceivably related to their disposition.
After repeated application (0.4μg/100mg ointment/hdad/day for 7days), the plasma level were slightly lower and the tissue distribution was almost the same in comparison with the single application.