Patient Factors Influencing Intraocular Penetration of Brimonidine-Related Eye Drops in Adults: A Post Hoc Pooled Analysis

INTRODUCTION: The factors related to the ocular penetration of drugs after the administration of eye drops in humans have not been examined in detail. Therefore, this study assessed the influence of patient factors on the intraocular penetration of eye drops. METHODS: A pooled analysis was performed on the data of 42 participants from three studies to evaluate the ocular pharmacokinetics in humans after the topical application of brimonidine-related eye drops. The patients were scheduled for vitrectomy and received brimonidine-related eye drops (0.1% brimonidine tartrate ophthalmic solution, 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution, or 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination suspension) twice daily for 1 week. We analyzed the effects of patient factors (sex, the presence or absence of lens, age, corneal thickness, corneal endothelial cell density, tear secretion, eye axial length, height, weight and body mass index [BMI]) on brimonidine, timolol and brinzolamide concentrations in the aqueous and vitreous humor after topical application. RESULTS: The drug concentrations in the aqueous and vitreous humor were not significantly different, regardless of sex or the presence or absence of lens. Age correlated positively with brimonidine (r = 0.3948, p = 0.012) and brinzolamide (r = 0.6809, p = 0.030) concentrations in the aqueous humor; the correlation with timolol showed a trend towards significance (r = 0.6425, p = 0.086). Corneal thickness, corneal endothelial cell density, tear secretion, eye axial length, height and BMI did not correlate with the drug concentrations in the aqueous or vitreous humor. Timolol concentration in the vitreous humor was negatively correlated with weight (r = − 0.8333, p = 0.010). CONCLUSION: The findings of this study emphasize the necessity of considering individual differences in ocular pharmacokinetics during drug therapy (formulation design of the eye drops and dose regimen).