ABSTRACT
Sublingual administration of carteolol or instillation into one eye reduces intraocular pressure (IOP) in both eyes. This suggests that carteolol absorbed systemically can reduce IOP and that the extra-ophthalmic route (e.g., the nasal route) can be an alternative method of drug administration. The authors compared the differences between ocular and nasal instillation relating to the pharmacokinetic and pharmacodynamic effects of a carteolol-ophthalmic solution on IOP and heart rate (HR) in a randomized, double-blind, crossover, placebo-controlled design in 11 healthyyoung extensive metabolizers for CYP2D6. The tmax, Cmax, and AUC0-t of carteolol (0.8 mg) instilled into the nostril were significantly higher than those into the eye (p < 0.05): tmax (h) = 0.25 (0.17-5.0),1.0 (0.17-5.0) (median value with range in the parenthesis, ocular vs. nasal); Cmax (ng/ml) = 1.33 +/- 1.57, 2.29 +/- 2.09; and AUC0-t (ng x h/ml) = 9.36 +/- 2.04, 21.13 +/- 1.58 (geometric mean +/- SD, ocular vs. nasal). The reduction of IOP after ocular instillation persisted significantly longer than that of nasal instillation (p < 0.05). The HR was significantly reduced after both ocular and nasal instillation (p < 0.05), although there were no significant differences between them. In conclusion, ocular instillation of a carteolol-ophthalmic solution has advantages over nasal instillation in controlling IOP and the potential to decrease adverse reactions due to lower plasma concentrations.
