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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Pharmacokinetics and metabolism of a vitamin D analogue (Seocalcitol) in rat and minipig.

1. Seocalcitol (EB 1089), a vitamin D analogue with strong antiproliferative effects in vitro and in vivo, is presently under clinical evaluation for the systemic treatment of various solid tumours. 2. The aim was to investigate the pharmacokinetics of Seocalcitol after single and multiple oral administration to rat and minipig. Furthermore, the hepatic metabolism of Seocalcitol was studied both in vitro and in vivo. In vitro metabolism was also investigated in human. 3. In rat, the pharmacokinetic profile of Seocalcitol (Cmax, AUC, Tmax, T(1/2)) was the same after single and oral administration. Pharmacokinetics were also demonstrated as dose-independent. The same was more difficult to evaluate in the minipig due to a great variation among individual animals. 4. In the male rat, the serum T(1/2) was 3 h, but in the female rat and minipig (both genders) T(1/2) = 8 h. 5. At Tmax the concentration of Seocalcitol in the liver (both species) was 10-fold higher than the concentration in serum. The major metabolites in the liver were various isomers of 26-hydroxy Seocalcitol, although the concentration of the individual isomers in rat and minipig were not the same. 6. The same metabolites were formed in vitro following incubations with rat, minipig and human S9 fractions.[1]

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