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The Clearance and Metabolism of Biotin Administered Intravenously to Pigs in Tracer and Physiologic Amounts Is Much More Rapid than Previously Appreciated^{1 ,2}

Departments of Biochemistry & Molecular Biology & Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, AR 72205 and ^* Department of Pediatrics and Pharmacology, University of Missouri at Kansas City and Division of Pediatric Clinical Pharmacology and Toxicology, The Children’s Mercy Hospital, Kansas City, MO 64108-9898

⁴To whom correspondence should be addressed. E-mail: mockdonaldm{at}uams.edu.

Understanding of biotin pharmacokinetics and regulation of metabolism is essential for the determination of the biotin requirement for humans. Using Landrace-Cambrough pigs as a model, we initially demonstrated that biotin binding to protein accounts for only a small percentage of the total biotin in plasma. A physiologic amount of [¹⁴C]biotin was administered intravenously to three pigs; nine blood samples were collected over 48 h. Plasma concentrations of ¹⁴C-labeled metabolites were negligible for the first 2 h after biotin infusion. Disappearance curves of total ¹⁴C and of [¹⁴C]biotin were similar; both fit a triexponential function consistent with a three-compartment, open model. To characterize the rapid early phase of disappearance more precisely, a physiologic amount of [¹⁴C]biotin was administered intravenously to five pigs; eight blood samples were collected over the first hour and 16 total samples over 48 h. Again a triexponential function provided an excellent fit. The mean half-life values (± 1 SD) for the three phases were 0.11 ± 0.07, 1.43 ± 0.42 and 22 ± 4 h. The [¹⁴C]biotin accumulated primarily in the liver, kidney and muscle. When administered intravenously at tracer doses to three pigs, [³H]biotin exhibited similar early pharmacokinetics; however, substantial quantities of a ³H-labeled metabolite appeared after 1 h. These studies provide evidence that egress of biotin from plasma is more rapid than previously appreciated. The slower second and third phases may represent transport into the cytosol, biotransformation into intermediates and covalent binding to intracellular proteins. Similar pharmacokinetics are likely to be seen in humans.

KEY WORDS: • biotin • pharmacokinetics • pigs • tissue distribution • metabolites

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