Nasal and conjunctival contributions to the systemic absorption of topical timolol in the pigmented rabbit: implications in the design of strategies to maximize the ratio of ocular to systemic absorption.
The primary purpose of this study was to determine the relative contribution of the nasal and the conjunctival mucosae to the systemic absorption of topically applied timolol in the pigmented rabbit. The nasal mucosa was found to be about 2.5 times more efficient than the conjunctival mucosa in contributing to systemic timolol absorption, which occurred to the extent of 74% of the instilled dose. In addition, a minimum of 5-10 min prolongation of ocular contact time was determined to be necessary for significantly reducing systemic drug absorption and indirectly enhancing ocular drug absorption. The pharmaceutical implication of this finding is that ophthalmic vehicles such as polymeric inserts and gels would provide more favorable ocular to systemic drug absorption ratios than vehicles such as aqueous solutions and low-viscosity polymer solutions.
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D003228:Conjunctiva / Q000378:metabolism*; D007262:Infusions, Intravenous; D009092:Mucous Membrane / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D009301:Nasolacrimal Duct / Q000378:metabolism; D009994:Osmolar Concentration; D011817:Rabbits; D013997:Time Factors; D013999:Timolol / Q000097:blood / Q000493:pharmacokinetics*
D013999:Timolol