Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
Folia Neuropathol. 2024;62(2):120-126. doi: 10.5114/fn.2024.140501.
Cytidine-5'-diphosphocholine (CDP-choline) is a key precursor for the intracellular synthesis of phosphatidylcholine and other phospholipids. Following either intravenous or oral application citicoline (CDP-choline of exogenous origin) undergoes quick decomposition to cytidine and choline, and for this reason it is frequently considered a prodrug. However, upon acute intravenous application in mice citicoline is, on a molar basis, 20 times less toxic than choline. To find out whether cytidine may attenuate toxicity of choline, in the present experiments we compared maximum tolerated doses of single intravenous injections of choline and equimolar mixture of choline and cytidine. We assumed that, if after oral intake a substantial part of citicoline is catabolised already in the intestine and its catabolites enter blood separately, intravenously applied equimolar mixture of cytidine and choline will be markedly less toxic than an equivalent molar dose of choline. However, the maximum tolerated single doses determined in our experiment for choline and equimolar mixture of choline and cytidine were similar. These data suggest that citicoline taken orally is not significantly decomposed in the intestinal lumen, but absorbed to blood as the intact molecule.
胞苷-5'-二磷酸胆碱（CDP-胆碱）是细胞内合成磷脂酰胆碱和其他磷脂的关键前体。无论是静脉内还是口服应用，胞磷胆碱（外源性 CDP-胆碱）都会迅速分解为胞苷和胆碱，因此它通常被认为是前体药物。然而，在急性静脉内应用于小鼠时，胞磷胆碱的毒性比胆碱低 20 倍，按摩尔计算。为了了解胞苷是否可以减轻胆碱的毒性，在本实验中，我们比较了单次静脉注射胆碱和等摩尔混合的胆碱和胞苷的最大耐受剂量。我们假设，如果胞磷胆碱在口服摄入后，其大部分在肠道中已经被代谢，其代谢产物分别进入血液，那么静脉内给予等摩尔混合的胞苷和胆碱将比等摩尔剂量的胆碱毒性显著降低。然而，我们实验中确定的胆碱和等摩尔混合的胆碱和胞苷的最大耐受单剂量相似。这些数据表明，口服摄入的胞磷胆碱在肠腔中没有明显分解，而是作为完整的分子被吸收到血液中。
