PT  - JOURNAL ARTICLE
AU  - Noriyuki Kasai
AU  - Toshiyuki Sakaki
AU  - Raku Shinkyo
AU  - Shin-ichi Ikushiro
AU  - Takashi Iyanagi
AU  - Miho Ohta
AU  - Kuniyo Inouye
TI  - METABOLISM OF 26,26,26,27,27,27-F<sub>6</sub>-1α,23<em>S</em>,25-TRIHYDROXYVITAMIN D<sub>3</sub> BY HUMAN UDP-GLUCURONOSYLTRANSFERASE 1A3<sup>*</sup>
AID  - 10.1124/dmd.104.002303
DP  - 2005 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 102--107
VI  - 33
IP  - 1
4099  - http://dmd.aspetjournals.org/content/33/1/102.short
4100  - http://dmd.aspetjournals.org/content/33/1/102.full
SO  - Drug Metab Dispos2005 Jan 01; 33
AB  - 26,26,26,27,27,27-Hexafluoro-1α,25-dihydroxyvitamin D3 [F6-1α, 25(OH)2D3], which is now clinically used as a drug for secondary hyperparathyroidism, is a hexafluorinated analog of the active form of vitamin D3. Our previous studies demonstrated that CYP24A1 is responsible for the metabolism of F6-1α,25(OH)2D3 in the target tissues and that F6-1α,25(OH)2D3 was successively converted to F6-1α,23S,25(OH)3D3 and F6-23-oxo-1α,25(OH)2D3. In this study, we examined the metabolism of F6-1α,25(OH)2D3,F6-1α,23S,25(OH)3D3, and F6-23-oxo-1α,25(OH)2D3 by human UDP-glucuronosyltransferases (UGTs). Of these compounds, F6-1α,23S,25(OH)3D3 was remarkably glucuronidated both in human liver microsomes and in the recombinant system expressing human UGT. No significant interindividual differences were observed among 10 human liver samples. The recombinant system for 12 species of human UGTs revealed that F6-1α,23S,25(OH)3D3 glucuronidation was specifically catalyzed by UGT1A3. The information obtained in this study seems very useful to predict the metabolism and efficacy of vitamin D analogs in human bodies before clinical trials. In addition, note that for the first time a possible probe substrate for UGT1A3 has been found. The American Society for Pharmacology and Experimental Therapeutics