The Metabolite Profile of Radioisotope-Labeled Biotin in Rats Indicates that Rat Biotin Metabolism is Similar to that in Humans

Abstract

The egg white-fed rat is the most commonly used animal model of human biotin deficiency. We sought to determine whether the urinary excretion rates of biotin and biotin metabolites in rats are similar to those reported in humans. D-(Carbonyl-14C)biotin was injected intraperitoneally at physiologic doses in 6- to 10-wk-old rats; HPLC and radiometric flow detection were used to specifically identify and quantify biotin and metabolites in urine. Substantial amounts of bisnorbiotin and biotin sulfoxide, the two principal human metabolites, were detected. The excretion rates of biotin and metabolites were strikingly dependent on the dose of biotin. When the dose of [14C]biotin was 30% of the daily dietary intake (a physiologic dose), 50% of the administered 14C was excreted within 24 h; more than half of the excretion was the unchanged vitamin. After d 1, [14C]bisnorbiotin was the major form excreted. For the cumulative 5-d excretion, [14C]biotin accounted for 46 ± 9%, [14C]bisnorbiotin accounted for 47 ± 11%, and [14C]biotin sulfoxide accounted for 8 ± 4% of the total of biotin, bisnorbiotin, and biotin sulfoxide recovered radioactivity (mean ± 1 SD, n = 6). These proportions are similar to those reported in humans: biotin = 52 ± 12%, bisnorbiotin = 35 ± 9%, and biotin sulfoxide = 13 ± 4% of total biotin plus metabolites (mean ± 1 SD, n = 10). Thus, these, studies confirm the earlier identification of bisnorbiotin and biotin sulfoxide as the two principal biotin metabolites and provide evidence that the rat is an appropriate model for human biotin metabolism.