Pharmacokinetic studies of 1.ALPHA.,24(R)-(OH)2D3(TV-02)(3). Absorption, distribution and excretion after a single or continuous transcutaneous application to rats.
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The excretion, plasma profiles and tissue distribution of <SUP>3</SUP>H-TV-02 ([1β-<SUP>3</SUP>H]-1α, 24(R)-(OH)<SUB>2</SUB>D<SUB>3</SUB>) were investigated in rats after a single and continuous (7days) transcutaneous application.<BR>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.<BR>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.<BR>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.<BR>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.
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