The clearance and metabolism of biotin administered intravenously to pigs in tracer and physiologic amounts is much more rapid than previously appreciated

Understanding of biotin pharmacokinetics and regulation of metabolism is es sential for the determination of the biotin requirement for humans, Using L andrace-Cambrough pigs as a model, we initially demonstrated that biotin bi nding to protein accounts for only a small percentage of the total biotin i n plasma. A physiologic amount of [C-14]biotin was administered intravenous ly to three pigs; nine blood samples were collected over 48 h. Plasma conce ntrations of C-14-labeled metabolites were negligible for the first 2 h aft er biotin infusion. Disappearance curves of total C-14 and of [C-14]biotin were similar; both fit a triexponential function consistent with a three-co mpartment, open model. To characterize the rapid early phase of disappearan ce more precisely, a physiologic amount of [C-14]biotin was administered in travenously to five pigs; eight blood samples were collected over the first hour and 16 total samples over 48 h. Again a triexponential function provi ded an excellent fit. The mean half-life values (+/- 1 SD) for the three ph ases were 0.11 +/- 0.07, 1.43 +/- 0.42 and 22 +/- 4 h. The [C-14]biotin acc umulated primarily in the liver, kidney and muscle. When administered intra venously at tracer doses to three pigs, [H-3]biotin exhibited similar early pharmacokinetics; however, substantial quantities of a H-3-labeled metabol ite appeared after 1 h. These studies provide evidence that egress of bioti n from plasma is more rapid than previously appreciated. The slower second and third phases may represent transport into the cytosol, biotransformatio n into intermediates and covalent binding to intracellular proteins. Simila r pharmacokinetics are likely to be seen in humans.