The effect of the low blink rate in rabbits on topical drug penetration.
OBJECTIVE
The low rate of blinking in the rabbit as compared to the human suggests that there may be a greater contact time for drugs applied topically in the animal. However, there have been no experiments performed to examine this belief directly.


METHODS
A small drop containing either fluorescein or FITC Dextran was applied to the eye of a rabbit without the use of tranquilizer or anesthetic. Subsequently, the change in the fluorescence of the precorneal tear film was followed with a noninvasive fluorometer.


CONCLUSIONS
The animal did not blink for 20-30 min. after the instillation. With either fluorophore, the tear film fluorescence remained constant after the first few minutes and fell precipitously at the first blink. Comparison with the loss kinetics in the human eye, an exponential decline with an average rate constant of 0.16 min-1, indicates that the AUC will be 3 times greater in the rabbit, and the penetration of a drug can be overestimated to the same degree from the low blink rate alone. There was a rise in the corneal fluorescence, attributable to penetration of the fluorophore, after the eye was washed at the end of the experiment. This was used to estimate the epithelial permeability which averaged 1.5 x 10(-4) cm hr for fluorescein and 1.9 x 10(-5) cm hr-1 for FITC Dextran. For most drugs, however, the epithelial permeability is sufficiently high that all the material present in the tear film will partition into the cornea in a few minutes. Considerations of contact time become irrelevant under these circumstances.
Maurice
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Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D001767:Blinking / Q000502:physiology*; D002463:Cell Membrane Permeability; D003315:Cornea / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D019793:Fluorescein; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005452:Fluoresceins / Q000493:pharmacokinetics*; D015590:Fluorophotometry; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D013666:Tears / Q000378:metabolism
D003911:Dextrans; D005452:Fluoresceins; D009883:Ophthalmic Solutions; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein