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  • Title: Ocular penetration of topical Delta9-tetrahydrocannabinol from rabbit corneal or cul-de-sac application site.
    Author: Green KE, Kearse CE.
    Journal: Curr Eye Res; 2000 Jul; 21(1):566-70. PubMed ID: 11035538.
    Abstract:
    PURPOSE: To determine the relative effects of low-volume drop placement either on the corneal surface or in the lower cul-de-sac on Delta9-tetrahydrocannabinol (THC) penetration into ocular fluids and tissues. METHODS: Pigmented rabbits received 10 microl drops in one eye at either application site. Care was taken to ensure that the drop remained at the site of drug placement. At different intervals after drop administration containing ( 3)H-Delta9-tetrahydrocannabinol in combination with either alpha-cyclodextrin or hydroxypropylmethylcellulose as excipients in different vehicles, eye fluids and tissues were harvested, digested, sampled and counted. RESULTS: Greater quantities of THC were found in the corneal epithelium, stroma/endothelium and aqueous humor of treated eyes after corneal drug application relative to values obtained after cul-de-sac drug application. Cul-de-sac applications gave higher values for inferior bulbar conjunctiva compared with corneal application. These results occurred for each vehicle despite a quantitative difference in drug penetration between the two vehicles. No THC was found in untreated contralateral eyes. CONCLUSIONS: Application of a lipophilic drug to the rabbit corneal surface exposed in the interpalpebral space produced higher tissue and fluid drug concentrations in the anterior segment of the eye compared with drug application into the lower cul-de-sac. This observation has relevance to pre-clinical drug toxicity testing as well as drop placement in patients for the treatment of ocular diseases.
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