RT Journal Article
SR Electronic
T1 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>
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 102
OP 107
DO 10.1124/dmd.104.002303
VO 33
IS 1
A1 Noriyuki Kasai
A1 Toshiyuki Sakaki
A1 Raku Shinkyo
A1 Shin-ichi Ikushiro
A1 Takashi Iyanagi
A1 Miho Ohta
A1 Kuniyo Inouye
YR 2005
UL http://dmd.aspetjournals.org/content/33/1/102.abstract
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