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The Metabolite Profile of Radioisotope-Labeled Biotin in Rats Indicates that Rat Biotin Metabolism is Similar to that in Humans^1,2,3,

Department of Pediatrics, Division of Digestive, Endocrine, Genetic, and Nutritional Disorders, University of Arkansas for Medical Sciences, and Arkansas Children's Hospital Research Institute, Little Rock, AR 72202-3591

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.

KEY WORDS: • biotin • biotin metabolite • rats • urine

¹ Presented at two meetings: Experimental Biology 95, April 1995, Atlanta, GA [Wang, K. S., Patel, A. & Mock, D. M. (1995) Excretion rates and metabolic profile of radioisotope labeled biotin in the rat. FASEB J. 9: A155 (abs.)] and The Southern Society of Pediatric Research, February 1995, New Orleans, LA [Wang, K. S., Patel, A. & Mock, D. M. (1995) Excretion rates and metabolic profile of radioisotope labeled biotin in the rat. J. Invest. Med. 43: A55 (abs.)].

² Supported by a grant from the National Institutes of Health to D.M.M. (DK36823).

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 27 November 1995. Revision accepted 1 April 1996.