Coburn S P, Mahuren J D
J Biol Chem. 1976 Mar 25;251(6):1646-52.
In rats 80 to 95% of 4'-deoxypyridoxine administered intraperitoneally, intravenously, intramuscularly, or subcutaneously was excreted in the urine within 7.5 hours. Orally administered deoxypyridoxine was also rapidly eliminated. Over one-half of the excreted material appeared as deoxypyridoxine-3-(hydrogen sulfate) and the remainder as unchanged deoxypyridoxine. Tissue concentrations of deoxypyridoxine 5'phosphate were comparable to those of pyridoxal 5'phosphate. In normal men about 50% of a single oral dose (3 to 7.5 mg/kg of body weight) appeared in the urine within 6 hours. 4'Deoxy-5-pyridoxic acid accounted for 50 to 100% of the excreted material. The remainder was unchanged deoxypyridoxine. No deoxypyridoxine-3-(hydrogen sulfate) was detected in human urine and no 4'-deoxy-5-pyridoxic acid was found in rat urine. Deoxypyridoxine 5'-phosphate was not detected in the urine of either species. The complexity of deoxypyridoxine metabolism indicated by these data suggests the use of caution in extrapolating data obtained with deoxypyridoxine to B6 metabolism in the absence of deoxypyridoxine, and particularly in extrapolating results from the rat to man. Synthesis for 4'-deoxypyridoxine-3-(ethyl carbonate), 4'-deoxypyridoxine 5'-acetate, 4'-deoxy-3-0-(2-sulfoethyl)-pyridoxine, and the metabolites are presented. These synthesis were facilitated by using ethylchloroformate conjugates and N-methylpiperazine hydrolysis to block and unblock the phenol group.
给大鼠腹腔内、静脉内、肌肉内或皮下注射4'-脱氧吡哆醇后，7.5小时内80%至95%的药物经尿液排出。口服脱氧吡哆醇也能迅速消除。排出物质中超过一半以脱氧吡哆醇-3-（硫酸氢盐）形式出现，其余为未变化的脱氧吡哆醇。脱氧吡哆醇5'-磷酸的组织浓度与吡哆醛5'-磷酸相当。正常男性单次口服剂量（3至7.5毫克/千克体重）约50%在6小时内出现在尿液中。4'-脱氧-5-吡啶酸占排出物质的50%至100%。其余为未变化的脱氧吡哆醇。人尿中未检测到脱氧吡哆醇-3-（硫酸氢盐），大鼠尿中未发现4'-脱氧-5-吡啶酸。两种动物的尿液中均未检测到脱氧吡哆醇5'-磷酸。这些数据表明的脱氧吡哆醇代谢复杂性提示，在将脱氧吡哆醇获得的数据外推至无脱氧吡哆醇时的维生素B6代谢，尤其是从大鼠外推至人时，应谨慎行事。文中介绍了4'-脱氧吡哆醇-3-（碳酸乙酯）、4'-脱氧吡哆醇5'-乙酸酯、4'-脱氧-3-O-（2-磺乙基）-吡哆醇及其代谢产物的合成方法。通过使用氯甲酸乙酯共轭物和N-甲基哌嗪水解来封闭和解除酚基团，促进了这些合成反应。
