Human vitreous concentrations of citicoline following topical application of citicoline 2% ophthalmic solution

Abstract

PurposeTo evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo.MethodsTwenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography.ResultsThe overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 μg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 μg/mL, 44.45 ± 10.19 μg/mL and 330.41 ± 75.8 μg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 μg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 μg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 μg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 μg/mL, 6.24 ± 3.6 μg/mL and 172.80 ± 99.76 μg/mL, respectively.ConclusionCiticoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.

Can Treatment With Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-controlled Clinical Trial

“… 30 Sufficient bioavailability of citicoline at the site of action to the retina was demonstrated in both animal 31 and human studies. 32 Parisi et al 12 could show that the addition of citicoline to IOP-lowering treatment was associated with an improvement in the electrophysiological function of the retina in glaucoma patients. Such an effect was clearly measurable after 4 months of treatment, but regressed to normality after citicoline was stopped during the wash-out, suggesting a neuroenhancer action of the molecule.…”

Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 3-year Pilot Study Evaluating Morpho-Functional Retinal Changes

“…These pieces of evidence raise a question regarding the possibility that citicoline administration through eye drops may target RGCs, and further studies are needed to clarify this point. Nevertheless, a recent study [24] on human eyes that underwent treatment with citicoline eye drops before vitreoretinal surgery [25,26] suggest that when citicoline is administered by eye drops, it can cause direct functional changes of the RGCs. Such functional changes may be due to the different properties of citicoline that affect neuroenhancement, neuroprotection, and neuroregeneration, and a recent review by Faiq et al described these phenomena in detail [21].…”

Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review

“…Furthermore, the administration of the drug following the topical application of citicoline 2% ophthalmic solution has recently allowed for detecting the intact drug, together with its metabolites, at a high concentration in the humor vitreous of human subjects, implying that neuroprotection can also likely be achieved in human subjects also with the intact molecule in vivo [ 26 ].…”

“…Thus, a formulation of citicoline by eye drops was developed that contained a solution of 2% of citicoline in addition to hyaluronic acid and benzalkonium chloride (OMK1 ® , Omikron Italia, Rome, Italy) or without benzalkonium chloride in Liposomal Formulation (OMK1-LF ® , Omikron Italia, Rome, Italy). Two studies, performed in mice [ 72 ] and in humans [ 26 ], respectively, documented a significant concentration of citicoline and its metabolites in the vitreous chamber after eye drops administration.…”