Human Vitreous Concentrations of Citicoline Following Topical Application of Citicoline 2% Ophthalmic Solution

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Nov 15

PMID 31725734

Citations 8

Authors

Carmela Carnevale

Gianluca Manni

Gloria Roberti

Alessandra Micera

Luca Bruno

Andrea Cacciamani

Romeo Altafini

Luciano Quaranta

Luca Agnifili

Lucia Tanga

Ivano Riva

Francesco Oddone

Affiliations

Soon will be listed here.

Abstract

Purpose: To 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.

Methods: Twenty-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.

Results: The 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.

Conclusion: Citicoline 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.

Citing Articles

Efficacy of citicoline as a supplement in glaucoma patients: A systematic review.

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Citicoline: pharmacological and clinical review, 2022 update.

Secades J, Gareri P Rev Neurol. 2022; 75(s05):S1-S89.

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Intact quantitative bioanalytical method development and fit-for-purpose validation of a monoclonal antibody and its related fab fragment in human vitreous and aqueous humor using LC-HRMS.

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Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review.

Oddone F, Rossetti L, Parravano M, Sbardella D, Coletta M, Ziccardi L Pharmaceuticals (Basel). 2021; 14(3).

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[The role of citicoline in glaucoma].

Junemann A, Grieb P, Rejdak R Ophthalmologe. 2021; 118(5):439-448.

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References

Gareri P, Castagna A, Cotroneo A, Putignano D, Conforti R, Santamaria F . The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer's Disease Study. J Alzheimers Dis. 2016; 56(2):557-565. DOI: 10.3233/JAD-160808. View

Secades J, Lorenzo J . Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol. 2006; 28 Suppl B:1-56. View

Spierer O, Regenbogen M, Lazar M, Yatziv Y . Effect of Corneal Thickness on the Penetration of Topical Vancomycin. Optom Vis Sci. 2015; 92(10):1027-31. DOI: 10.1097/OPX.0000000000000692. View

Rejdak R, Toczolowski J, Solski J, Duma D, Grieb P . Citicoline treatment increases retinal dopamine content in rabbits. Ophthalmic Res. 2002; 34(3):146-9. DOI: 10.1159/000063658. View

Fresina M, Dickmann A, Salerni A, De Gregorio F, Campos E . Effect of oral CDP-choline on visual function in young amblyopic patients. Graefes Arch Clin Exp Ophthalmol. 2007; 246(1):143-50. DOI: 10.1007/s00417-007-0621-6. View

Parisi V, Coppola G, Ziccardi L, Gallinaro G, Falsini B . Cytidine-5'-diphosphocholine (Citicoline): a pilot study in patients with non-arteritic ischaemic optic neuropathy. Eur J Neurol. 2008; 15(5):465-74. DOI: 10.1111/j.1468-1331.2008.02099.x. View

Parisi V, Manni G, Colacino G, Bucci M . Cytidine-5'-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology. 1999; 106(6):1126-34. DOI: 10.1016/S0161-6420(99)90269-5. View

Secades J, Alvarez-Sabin J, Castillo J, Diez-Tejedor E, Martinez-Vila E, Rios J . Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials. J Stroke Cerebrovasc Dis. 2016; 25(8):1984-96. DOI: 10.1016/j.jstrokecerebrovasdis.2016.04.010. View

Kaur I, Smitha R . Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev Ind Pharm. 2002; 28(4):353-69. DOI: 10.1081/ddc-120002997. View

10.

Secades J . Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol. 2011; 52 Suppl 2:S1-S62. View

11.

Ottobelli L, Manni G, Centofanti M, Iester M, Allevena F, Rossetti L . Citicoline oral solution in glaucoma: is there a role in slowing disease progression?. Ophthalmologica. 2013; 229(4):219-26. DOI: 10.1159/000350496. View

12.

Connolly G, Duley J . Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol Sci. 1999; 20(5):218-25. DOI: 10.1016/s0165-6147(99)01298-5. View

13.

Agnoli A, Ruggieri S, Denaro A, Bruno G . New strategies in the management of Parkinson's disease: a biological approach using a phospholipid precursor (CDP-choline). Neuropsychobiology. 1982; 8(6):289-96. DOI: 10.1159/000117914. View

14.

Martinez-de-la-Casa J, Rayward O, Saenz-Frances F, Santos-Bueso E, Mendez-Hernandez C, Herrero-Vanrell R . Effects of corneal thickness on the intraocular penetration of travoprost 0.004%. Eye (Lond). 2012; 26(7):972-5. PMC: 3396174. DOI: 10.1038/eye.2012.74. View

15.

Bogdanov P, Sampedro J, Sola-Adell C, Simo-Servat O, Russo C, Varela-Sende L . Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration. Int J Mol Sci. 2018; 19(8). PMC: 6121526. DOI: 10.3390/ijms19082458. View

16.

Park C, Kim Y, Noh H, Cheon E, Yang Y, Yoo J . Neuroprotective effect of citicoline against KA-induced neurotoxicity in the rat retina. Exp Eye Res. 2005; 81(3):350-8. DOI: 10.1016/j.exer.2005.02.007. View

17.

Matteucci A, Varano M, Gaddini L, Mallozzi C, Villa M, Pricci F . Neuroprotective effects of citicoline in in vitro models of retinal neurodegeneration. Int J Mol Sci. 2014; 15(4):6286-97. PMC: 4013628. DOI: 10.3390/ijms15046286. View

18.

Roberti G, Tanga L, Michelessi M, Quaranta L, Parisi V, Manni G . Cytidine 5'-Diphosphocholine (Citicoline) in Glaucoma: Rationale of Its Use, Current Evidence and Future Perspectives. Int J Mol Sci. 2015; 16(12):28401-17. PMC: 4691046. DOI: 10.3390/ijms161226099. View

19.

Roberti G, Tanga L, Parisi V, Sampalmieri M, Centofanti M, Manni G . A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy. Indian J Ophthalmol. 2014; 62(5):549-53. PMC: 4065503. DOI: 10.4103/0301-4738.133484. View

20.

Kent A, Nussdorf J, David R, TYSON F, Small D, Fellows D . Vitreous concentration of topically applied brimonidine tartrate 0.2%. Ophthalmology. 2001; 108(4):784-7. DOI: 10.1016/s0161-6420(00)00654-0. View