Cravedi J P, Baradat M, Debrauwer L, Alary J, Tulliez J, Bories G
Laboratoire des Xénobiotiques, INRA, Toulouse, France.
Drug Metab Dispos. 1994 Jul-Aug;22(4):578-83.
Following subcutaneous administration of [3H]chloramphenicol (CP) to duck, HPLC and TLC analyses showed that the two most important metabolites in 0- to 24-hr excreta were CP-oxamic acid and CP-alcohol, which together accounted for about one-third of the radioactivity therein. The remainder was due to unchanged CP (15% dose), CP-base (5% dose), and various metabolites representing < 4% dose each. Among these, CP-glucuronide and CP-sulfate have been previously isolated in mammals. In addition to these metabolites, several previously unreported in vivo CP biotransformation products were identified in this study by HPLC and MS comparison with synthetic reference compounds. These new metabolites were unequivocally identified as 1-O-monoacetyl CP, CP-1,3-diacetate, N-acetyl CP-base, CP-oxamylglycine, and CP-oxamylethanolamine. Besides these formally identified compounds, the CP-phosphate structure was tentatively assigned to a conjugate metabolite resistant to beta-glucuronidase and sulfatase hydrolysis. The possible origin of these metabolites is discussed extensively.
给鸭皮下注射[³H]氯霉素（CP）后，高效液相色谱（HPLC）和薄层色谱（TLC）分析表明，0至24小时排泄物中两种最重要的代谢产物是氯霉素草氨酸和氯霉素醇，它们合起来约占其中放射性的三分之一。其余部分归因于未变化的CP（剂量的15%）、氯霉素碱（剂量的5%）以及各自占比小于4%剂量的各种代谢产物。其中，氯霉素葡萄糖醛酸苷和氯霉素硫酸盐先前已在哺乳动物中分离得到。除了这些代谢产物外，本研究通过HPLC和与合成参考化合物的质谱比较，鉴定出了几种先前未报道的CP体内生物转化产物。这些新的代谢产物被明确鉴定为1-O-单乙酰氯霉素、氯霉素1,3-二乙酸酯、N-乙酰氯霉素碱、氯霉素草氨酰甘氨酸和氯霉素草氨酰乙醇胺。除了这些已正式鉴定的化合物外，氯霉素磷酸酯结构被初步归属于一种对β-葡萄糖醛酸酶和硫酸酯酶水解有抗性的共轭代谢产物。文中广泛讨论了这些代谢产物可能的来源。
