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Pharmacology: Citicoline is a pyrimidine 5'-nucleotide which serves as an essential precursor in the synthesis of lecithin (phosphatidylcholine) and other phospholipids.
Mechanism of Action: The extensive damage caused by stroke requires repair and regeneration of axons and synapses of neurons, so new membrane production is essential. The primary mechanism by which citicoline is believed to have a therapeutic effect in stroke is its ability to increase the synthesis of phosphatidylcholine, the primary neuronal membrane component. It also enhances acetylcholine synthesis, and might thus ameliorate symptoms caused by the stroke induced loss of cholinergic neurons.
Another mechanism by which citicoline may have a more acute effect on the outcome of stroke patients relates to its ability to reduce free fatty acid accumulation at the site of injury, and thus to prevent further damage.
Citicoline avoids, reduces or reverses the effects of ischemia and/or hypoxia in major part of animals and cellular models studied and acts in the cranial traumatic forms, reduces and limits the injuries to the membranes of the nerve cells, re-establishes the sensitivity and the function of the regulatory intracellular enzymes and accelerates the re-absorption of the cerebral edema.
Thus considerable evidence accumulated supports the use of citicoline for increasing and maintaining and repairing the membranes and the neuronal function in situations such as ischemia and traumatic injuries. In patients with senile dementia, citicoline reduces the evolution of damages.
Pharmacokinetics: Citicoline is well absorbed after oral administration. It has an absolute bioavailability of approximately 99%. Citicoline is metabolized in the liver to free choline. The liver is capable of synthesizing lecithin from choline, and resynthesizing citicoline from cytidine and choline.
Due to difficulties in detecting plasma levels of citicoline itself, assays have been performed for free choline or total plasma radioactivity in terms of citicoline equivalents. Plasma choline levels are elevated significantly after oral administration. Two peaks of plasma citicoline equivalents have been reported after oral doses of radiolabeled citicoline (300 mg). An initial peak is observed in approximately 1 hour (1.5 mcg/mL), presumably related to a mixture of unchanged citicoline and its metabolites (choline and cytidine diphosphate). A second peak of approximately 3 mcg/mL is seen 24 hours postdose, and may be due to delayed absorption of the drug or continued metabolite accumulation over this time period. Choline derived from citicoline crosses the blood brain barrier, presumably serving as a source for acetylcholine and phosphatidylcholine (lecithin) synthesis. The major portion of a dose of citicoline appears to be incorporated into tissues and/ or used in biosynthetic/biodegradation pathways, including lecithin/lipid membrane synthesis.
Small amounts of a dose are recovered in urine (2% to 3%) and in feces (less than 1%). Approximately 12% of a dose is eliminated as respiratory carbon dioxide. Elimination half life of citicoline is 3.5 hours (first peak concentration), 125 hours (second peak concentration).
