Guaitani A, Abbruzzi R, Bastone A, Bianchi M, Bonati M, Catalani P, Latini R, Pantarotto C, Szczawinska K
Toxicol Lett. 1987 Sep;38(1-2):55-66. doi: 10.1016/0378-4274(87)90111-1.
Caffeine metabolism to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was studied in the isolated, perfused rat liver. The [2-14C]-labelled drug and metabolites were separated by thin-layer chromatography or high-pressure liquid chromatography. The chemical structure of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was confirmed by mass spectrometry and it was quantitatively determined by liquid scintillation counting. 6-Amino-5-[N-methylformylamino]-1,3-dimethyluracil is one of the major metabolites of caffeine found in the perfusion medium. The kinetics of caffeine elimination and of the uracil metabolite formation were studied up to 2 h perfusion time using livers from control rats and rats pretreated with phenobarbital, beta-naphthoflavone or 3-methylcholanthrene. Phenobarbital pretreatment did not modify the rate of caffeine elimination or the extent of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil formation. In contrast, there was a highly significant inducing effect on both drug elimination and formation of the uracil metabolite in perfusions of livers from beta-naphthoflavone- and 3-methylcholanthrene-pretreated animals.
在离体灌注大鼠肝脏中研究了咖啡因代谢生成6-氨基-5-[N-甲基甲酰氨基]-1,3-二甲基尿嘧啶的过程。用薄层色谱法或高压液相色谱法分离[2-¹⁴C]标记的药物及其代谢产物。通过质谱法确认了6-氨基-5-[N-甲基甲酰氨基]-1,3-二甲基尿嘧啶的化学结构，并通过液体闪烁计数法对其进行了定量测定。6-氨基-5-[N-甲基甲酰氨基]-1,3-二甲基尿嘧啶是灌注介质中发现的咖啡因主要代谢产物之一。使用对照大鼠以及用苯巴比妥、β-萘黄酮或3-甲基胆蒽预处理的大鼠的肝脏，研究了长达2小时灌注时间内咖啡因消除和尿嘧啶代谢产物形成的动力学。苯巴比妥预处理并未改变咖啡因消除速率或6-氨基-5-[N-甲基甲酰氨基]-1,3-二甲基尿嘧啶的生成量。相反，在β-萘黄酮和3-甲基胆蒽预处理动物的肝脏灌注中，对药物消除和尿嘧啶代谢产物的形成均有高度显著的诱导作用。
