In vivo metabolism of the vitamin D analog, 22-oxacalcitriol: evidence for side-chain truncation and 17-hydroxylation.
After intravenous administration of the vitamin D3 analog, 22-oxacalcitriol (OCT), to normal rats plasma metabolites were investigated by HPLC, GC-MS and LC-MS. Five side-chain oxidation metabolites, 24R(OH)OCT, 24S(OH)OCT, (25R)-26(OH)OCT, (25S)-26(OH)OCT and 24oxoOCT, were identified by comparison with the corresponding synthetic compounds. These side-chain oxidation metabolites were similar to those of calcitriol [1alpha,25(OH)2 vitamin D3] described previously. Besides these five metabolites, two unique side-chain cleavage metabolites, 20S(OH)-hexanor-OCT and 17,20S(OH)2-hexanor-OCT, were identified as main metabolites in plasma by GC-MS and LC-MS using a specific chemical reaction. Our studies suggest that OCT is extensively metabolized and circulates in blood as a number of metabolites as well as unchanged OCT. This metabolism includes both unique pathways of C23-O22 cleavage and 17-hydroxylation, in addition to the side-chain oxidation metabolites similar to those of 1alpha,25-(OH)2D3.
Ishigai
M
M
Drug Metabolism and Pharmacokinetics Laboratory, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Arai
S
S
Ishitani
Y
Y
Kumaki
K
K
D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D006900:Hydroxylation; D008297:Male; D008956:Models, Chemical; D051381:Rats
D002117:Calcitriol; C051883:maxacalcitol