Arnaud M J, Bracco I, Sauvageat J L, Clerc M F
Toxicol Lett. 1983 May;16(3-4):271-9. doi: 10.1016/0378-4274(83)90187-x.
6-Amino-5[N-formylmethylamino]1,3[Me-14C]dimethyluracil (1,3,7-DAU), the most important caffeine metabolite in the rat and a minor one in man was synthesized and administered p.o. or i.v. to pregnant rats. This study demonstrates the distribution of this metabolite in the animal and its transfer to the embryos and the fetus. The fetus was shown to be protected by a placental barrier which leads to a lower fetal tissue exposure 1 h after the administration, the equilibrium between fetus and pregnant rat being reached 4-5 h later. Future studies testing the fetotoxicity of this metabolite compared with caffeine must take into consideration that only about half of the oral dose is absorbed. In addition, similar fetal tissue exposure must be obtained when this metabolite is given orally or is produced from caffeine.
6-氨基-5[N-甲酰甲基氨基]-1,3[甲基-¹⁴C]二甲基尿嘧啶（1,3,7-二甲基黄嘌呤），大鼠体内最重要的咖啡因代谢产物，在人体内则是次要代谢产物，已被合成并经口服或静脉注射给予怀孕大鼠。本研究证明了该代谢产物在动物体内的分布及其向胚胎和胎儿的转移。研究表明，胎盘屏障对胎儿起到了保护作用，给药后1小时胎儿组织暴露量较低，4至5小时后胎儿与怀孕大鼠之间达到平衡。未来在测试该代谢产物与咖啡因相比的胚胎毒性时，必须考虑到口服剂量只有约一半被吸收。此外，当口服该代谢产物或由咖啡因产生该代谢产物时，必须获得相似的胎儿组织暴露量。
