The tissue-specific distribution of 3H-seocalcitol (EB 1089) and 3H-calcitriol in rats.
Seocalcitol (EB 1089) is under development for the treatment of hepato-cellular carcinoma (HCC). The tissue distribution of 3H-seocalcitol was investigated in comparison to 3H-calcitriol in rats. Quantitative whole-body autoradiography was used to quantify the tissue distribution. The greatest difference in distribution between the two compounds was observed in the bloodstream. For most tissues the ratio seocalcitol/calcitriol varied between 0.2 and 3.1. The concentration of radioactivity in the liver was almost the same for the two compounds. For seocalcitol the concentration in the liver was 10 times higher than in serum. Assuming that the liver/serum concentration ratio is the same in rats and humans, the concentration of seocalcitol in the human liver is expected to be higher than the concentration resulting in more than 50% inhibition of cancer cell proliferation, and thus pharmacologically effective in HCC. It is questionable whether calcitriol would be present in the human liver in sufficient concentrations to be effective for the treatment of HCC, as the antiproliferative activity of calcitriol is generally more than 10-fold lower compared to that of seocalcitol and as calcitriol can only be administered at a dose that is ca. three-fold lower than the dose of seocalcitol.
Kissmeyer
Anne-Marie
AM
Biological Research, LEO Pharma, DK-2750 Ballerup, Denmark. anne.marie-kissmeyer@leo-pharma.com
Nielsen
Jeanet Løgsted
JL
Binderup
Lise
L
D000818:Animals; D001345:Autoradiography; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D014018:Tissue Distribution
D002117:Calcitriol; C078903:seocalcitol