RT Journal Article
SR Electronic
T1 Biliary and Urinary Metabolic Profiles of 1,2-Diethyl-3-hydroxypyridin-4-one (CP94) in the Rat
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 873
OP 879
VO 28
IS 8
A1 Shu L. Lu
A1 Itsaraet Gosriwatana
A1 Ding Y. Liu
A1 Zu D. Liu
A1 Anthony I. Mallet
A1 Robert C. Hider
YR 2000
UL http://dmd.aspetjournals.org/content/28/8/873.abstract
AB This study compares the biliary and urinary metabolic profiles of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), an orally active iron chelator, in the normal rat. Surprisingly, CP94 was found to form two phase II metabolites, the 3-O- and 4-O-glucuronides. These glucuronides accounted for 38 and 28% of the administered CP94 dose, in bile and urine, respectively. Unchanged CP94 accounted for 5% of the CP94 dose in both bile and urine. The 2-(1′-hydroxy) metabolite of CP94 was found to be the dominant metabolite in urine. In addition, an unstable metabolite was detected in the bile although its structure remains unknown at the present stage. The excretion of iron in bile, after administration of CP94, was found to parallel the biliary elimination of CP94 together with its hydroxylated derivatives, indicating the importance of metabolites in iron excretion. The American Society for Pharmacology and Experimental Therapeutics