Cytidine does not affect acute toxicity of intravenously administered choline
Kamil Synoradzki1, Maciej Swiatkiewicz1, Paweł Grieb1
1Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
Folia Neuropathologica
|August 21, 2024
Summary
Citicoline (cytidine diphosphate choline) is absorbed intact orally, not broken down into cytidine and choline in the gut. This suggests citicoline acts as a prodrug, delivering its components directly to the bloodstream.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Cytidine-5'-diphosphocholine (CDP-choline), known as citicoline, is a precursor for phospholipid synthesis.
- Exogenous citicoline is often considered a prodrug due to expected rapid breakdown into cytidine and choline.
- Previous studies indicated citicoline is less toxic than choline, prompting investigation into cytidine's potential protective role.
Purpose of the Study:
- To determine if cytidine can mitigate choline toxicity.
- To investigate the absorption and metabolic fate of orally administered citicoline.
Main Methods:
- Comparison of maximum tolerated doses (MTD) of intravenous choline versus an equimolar mixture of choline and cytidine in mice.
- Assessment of toxicity following single intravenous injections.
Main Results:
- The MTD for choline and the equimolar mixture of choline and cytidine were found to be similar.
- This indicates that co-administration of cytidine does not significantly reduce choline's acute toxicity in this model.
- The findings challenge the assumption of significant intestinal breakdown of citicoline.
Conclusions:
- Citicoline is likely absorbed into the bloodstream as an intact molecule after oral administration.
- The molecule is not substantially catabolized in the intestinal lumen prior to absorption.
- This supports the concept of citicoline acting as a prodrug that delivers both cytidine and choline intact.
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