Wang K S, Kearns G L, Mock D M
Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, AR 72205, USA.
J Nutr. 2001 Apr;131(4):1271-8. doi: 10.1093/jn/131.4.1271.
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.
了解生物素的药代动力学和代谢调节对于确定人类对生物素的需求量至关重要。我们以长白-坎布罗猪为模型，最初证明生物素与蛋白质的结合仅占血浆中总生物素的一小部分。给三头猪静脉注射生理剂量的[14C]生物素；在48小时内采集了九份血样。生物素输注后的前2小时，14C标记代谢物的血浆浓度可忽略不计。总14C和[14C]生物素的消失曲线相似；两者均符合三室开放模型的三指数函数。为了更精确地表征消失的快速早期阶段，给五头猪静脉注射生理剂量的[14C]生物素；在最初一小时内采集了八份血样，在48小时内共采集了16份血样。三指数函数再次提供了很好的拟合。三个阶段的平均半衰期值（±1 SD）分别为0.11±0.07、1.43±0.42和22±4小时。[14C]生物素主要在肝脏、肾脏和肌肉中蓄积。当以示踪剂量静脉注射给三头猪时，[3H]生物素表现出相似的早期药代动力学；然而，1小时后出现了大量的3H标记代谢物。这些研究提供了证据，表明生物素从血浆中的流出比之前认为的更快。较慢的第二和第三阶段可能代表转运到细胞质、生物转化为中间体以及与细胞内蛋白质的共价结合。人类可能也会出现类似的药代动力学。
