Vitreous and Aqueous Concentrations of Brimonidine Following Topical Application of Brimonidine Tartrate 0.1% Ophthalmic Solution in Humans

Takamura, Yoshihiro; Tomomatsu, Takeshi; Matsumura, Takeshi; Takihara, Yuji; Kozai, Seiko; Arimura, Shogo; Yokota, Satoshi; Inatani, Masaru

doi:10.1089/jop.2015.0003

Cited by 27 publications

(28 citation statements)

References 12 publications

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“…These results agree with a previous study by Takamura et al where the authors analyzed the vitreous and aqueous humor concentrations of brimonidine topical ophthalmic solution 0.1% by means of liquid chromatography and tandem mass spectrometry in 24 patients undergoing PPV for idiopathic ERM or macular hole [26]. The authors reported no significant differences of brimonidine concentration in the vitreous between phakic and pseudophakic eyes [26].…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 91%

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

et al. 2019

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“…Since the target tissue of the neuroprotective effect of brimonidine is the retina, it is important to investigate the drug distribution in the posterior parts of the eye after BMD/TIM administration. A previous study showed that, in most patients, topical multiple administration of BMD twice daily reached a brimonidine vitreous concentration [ 2 nM [33], which is the concentration necessary to activate the a 2adrenergic receptor [34]. In addition, Shinno et al [35] suggest that the brimonidine concentration in the vitreous body can be a surrogate indicator of the free concentration in the posterior retina/choroid, which is regarded as an available fraction for receptor binding.…”

Section: Groupmentioning

confidence: 99%

Ocular and Systemic Pharmacokinetics of Brimonidine and Timolol After Topical Administration in Rabbits: Comparison Between Fixed-Combination and Single Drugs

et al. 2020

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Introduction: This study was aimed to compare ocular tissue distribution and systemic exposure of brimonidine and timolol after single topical administration to rabbits of fixed-combination ophthalmic solution of 0.1% brimonidine tartrate and 0.5% timolol and single drugs (0.1% brimonidine tartrate ophthalmic solution or 0.5% timolol ophthalmic solution) or concomitant administration of single drugs. Methods: Rabbits were treated with a single topical administration of each ophthalmic solution or concomitant administration of single drugs. For concomitant administration, 0.1% brimonidine tartrate was administered after 0.5% timolol instillation successively within 10 s (without interval) or with 5-min intervals. Brimonidine and timolol concentrations in the aqueous humor, retina/choroid, vitreous body, and plasma were determined with liquid chromatography-tandem mass spectrometry.

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“…One may think that topical administration in mice often allows the drug to reach the retina much easier than larger animals, and argue that the current results may not be meaningful in human patients. However, recent study in humans reported that topically applied ophthalmic solution may penetrate into the vitreous more than we expect, and this may be independent of the lens status 19 . We previously reported that topical application of brimonidine, an α2-adrenergic receptor agonist, exerts neuroprotective effects in EAAC1 KO mice 20 .…”

Section: Discussionmentioning

confidence: 45%

Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury

Nishijima

Namekata

Kimura

et al. 2020

Sci Rep

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Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance. In this study, we examined if topical ripasudil has therapeutic potential in adult mice after optic nerve crush (ONC). Topical ripasudil suppressed ONC-induced phosphorylation of p38 mitogen-activated protein kinase and ameliorated RGC death. In addition, topical ripasudil significantly suppressed the phosphorylation of collapsin response mediator protein 2 and cofilin, and promoted optic nerve regeneration. These results suggest that topical ripasudil promotes RGC protection and optic nerve regeneration by modulating multiple signaling pathways associated with neural cell death, microtubule assembly and actin polymerization.

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Vitreous and Aqueous Concentrations of Brimonidine Following Topical Application of Brimonidine Tartrate 0.1% Ophthalmic Solution in Humans

Cited by 27 publications

References 12 publications

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

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

Ocular and Systemic Pharmacokinetics of Brimonidine and Timolol After Topical Administration in Rabbits: Comparison Between Fixed-Combination and Single Drugs

Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury

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