Concentrations of betaxolol in ocular tissues of patients with glaucoma and normal monkeys after 1 month of topical ocular administration

PURPOSE. To measure the concentration of betaxolol in tissues of humans with glaucoma and normal monkeys after topical administration. METHODS. Enucleated eyes (n = 7) of patients with glaucoma (age range, 27-79 years), without apparent anatomic disruption that would be likely to influence betaxolol absorption and intraocular distribution (exceptions: one pseudophakic, one aphakic) or other disease, were analyzed for betaxolol concentrations after self-administration of 0.25% betaxolol twice daily for 28 days or longer. The last instillation was made within 6 hours of surgery. Cynomolgus monkeys (n = 3) received 0.25% betaxolol twice daily unilaterally for 30 days. Betaxolol was measured by HPLC and tandem mass spectrometry (MS/MS) in plasma and ocular tissues. RESULTS. In humans, mean betaxolol concentrations (excluding the aphakic patient) were 71.4 ± 41.8 ng/g in the retina, 31.2 ± 14.8 ng/g in the optic nerve head, and 1290 ± 1170 ng/g in the choroid. Mean concentrations in the iris and ciliary body were 73,200 ± 89,600 and 4,250 ± 3,020 ng/g, respectively. Betaxolol concentration was higher in all ocular tissues than in the plasma (0.59 ± 0.32 ng/mL). In the monkeys the concentrations in the posterior tissues of the treated eyes were higher than in the untreated eyes, with mean differences in the retina and optic nerve head of 121 and 130 ng/g, respectively. CONCLUSIONS. Topically applied betaxolol was bioavailable to posterior ocular tissues, including the retina and optic nerve head, of patients with glaucoma and of normal cynomolgus monkeys. The higher betaxolol levels in the treated versus untreated monkey eyes are consistent with betaxolol's reaching posterior tissues by local absorption and distribution.