Purchase this article with an account.
Chinatsu Tosha, Sherri Decker, Guadalupe Ruiz, Octavio Avalos, Werhner Orilla, Larry Gruber, Ton Lin, Alexandra Almazan, Daniel Gil, James Burke; Ocular bioavailability of brimonidine 0.1% BID in non-human primates. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5072.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine whether topically applied Alphagan 0.1% BID in non-human primates would deliver sufficient brimonidine to the central retina to activate α2-adrenergic receptors for a neuroprotective effect.
Alphagan 0.1% (Allergan, Inc., Irvine, CA) was administered to one or both eyes of six female cynomolgus monkeys every 12 hours (BID; 9 eyes) for four weeks. Three contralateral eyes served as controls and received placebo. Animals were euthanized 2 hours following the final dose. Then, ocular tissues from anterior segments (aqueous humor (AH), iris and ciliary body (CB)) and from posterior segments (conjunctiva, peripheral sclera, vitreous humor, and tissues from a central 8 mm punch biopsy: neurosensory retina, underlying RPE/choroid, and sclera) were collected and assayed for brimonidine concentrations. The brimonidine plasma concentration was also analyzed to examine the possible systemic transfer of the drug.
The brimonidine concentrations in anterior segments were 189 ± 132 nM (AH), 29147 ± 7526 nM (iris) and 322560 ± 73384 nM (CB). The concentrations in posterior segments were 11062 ± 6027 nM (conjunctiva), 9565.4 ± 3927 nM (peripheral sclera), 47 ± 11 nM (vitreous), 122 ± 26 nM (central retina), 3,352 ± 1,017 nM (RPE/choroid) and 1,994 ± 465 nM (sclera). The plasma concentration of brimonidine in the bilaterally treated monkeys was 0.49 ± 0.43 nM. The retinal brimonidine concentrations in control untreated eyes were 16% of that of treated eyes. The brimonidine concentrations in anterior segments of control eyes were 29 ± 44 nM (AH), 1123 ± 523 nM (iris) and 15436 ± 10596 nM (CB). The concentrations in posterior segments of control eyes were 1808 ± 1675 nM (conjunctiva), 807 ± 428 nM (peripheral sclera), 807 ± 428 nM (vitreous), 807 ± 428 nM (central retina), 985 ± 319 nM (RPE/choroid) and 327 ± 295 nM (sclera).
This study indicates that Alphagan 0.1% BID delivers pharmacologically sufficient brimonidine to the central retina of non-human primates. The distribution of plasma and ocular tissue brimonidine concentrations suggests that delivery to the retina was via the periocular pathway; not via systemic transfer. The strong bonding of brimonidine to ocular melanin may allow a long retention of brimonidine in the pigmented ocular tissues after the topical administration. Melanin in choroid and RPE may play a major role in facilitating the delivery of brimonidine to the central retina.
This PDF is available to Subscribers Only