Vitreous and aqueous concentrations of brimonidine following topical application of brimonidine tartrate 0.1% ophthalmic solution in humans.
OBJECTIVE
To determine the vitreous and aqueous concentrations of brimonidine after topical application of the ophthalmic solution 0.1%.


METHODS
The prospective observational case series included patients with an idiopathic epiretinal membrane or macular hole who were scheduled for a pars plana vitrectomy. Brimonidine tartrate ophthalmic solution 0.1% was topically administered twice daily for 1 week preoperatively. Vitreous and aqueous humor was collected before vitrectomy, and then, the brimonidine concentration was measured with liquid chromatography tandem spectrometry (LC/MS/MS).


RESULTS
Twenty-four patients (19 phakic eyes and 5 pseudophakic eyes) were enrolled. The mean concentrations in the aqueous humor and vitreous were 336.0 ± 276.2 and 4.8 ± 3.2 nM, respectively. A significant relationship was observed between the vitreous and aqueous samples (P = 0.034, R(2) = 0.22). Nineteen (79%) of the 24 eyes showed more than 2 nM of brimonidine tartrate concentration in the vitreous. In the phakic eyes, the mean concentration of brimonidine in the vitreous was 4.9 ± 3.3 nM, while the mean concentration in the pseudophakic eyes was 4.1 ± 2.4 nM, demonstrating no significant difference between pseudophakic and phakic eyes (P = 0.59).


CONCLUSIONS
After 1 week of dosing, in most of the patients who topically received brimonidine tartrate 0.1%, the concentration in the vitreous of the molecule was above 2 nM, which is known to activate neuroprotective α-2 receptors in animal retina. The drug penetration into the vitreous seems to be independent of lens status.
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.
Yoshihiro
Y
Takamura
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.
Takeshi
T
Tomomatsu
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.
Takehiro
T
Matsumura
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.
Yuji
Y
Takihara
Seiko
S
Kozai
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.
Shogo
S
Arimura
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.|3Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Satoshi
S
Yokota
1Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui-ken, Japan.
Masaru
M
Inatani
D000287:Administration, Topical; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000368:Aged; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D000068438:Brimonidine Tartrate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D019773:Epiretinal Membrane / Q000188:drug therapy / Q000601:surgery; D005260:Female; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D051381:Rats; D012167:Retinal Perforations / Q000188:drug therapy / Q000601:surgery; D053719:Tandem Mass Spectrometry / Q000379:methods; D014821:Vitrectomy / Q000379:methods; D014822:Vitreous Body / Q000378:metabolism*
D058647:Adrenergic alpha-2 Receptor Agonists; D009883:Ophthalmic Solutions; D000068438:Brimonidine Tartrate