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Meibomian glands are modified sebaceous glands embedded within specific types of dense connective tissues. This study investigated drug penetration into meibomian glands following a single topical administration in rabbits. We measured time course concentrations of the selective glucocorticoid receptor agonist (SEGRA) SA22465 and betamethasone in lid margins, palpebral conjunctival epithelium, and meibomian glands following a single instillation using a newly established collection method. We also visualized the distribution of 14 C-SA22465 in eyelid tissue sections using microautoradiography. Concentrations of SA22465 and its major metabolite SA22313 were highest in lid margins, followed by palpebral conjunctival epithelium and meibomian glands in a 100-fold descending order. Betamethasone exhibited similar distribution profiles with smaller concentration differences. The distribution of silver grains as a quantitative index of radioactivity in eyes and eyelids was determined in a subjective manner using microautoradiographs, which revealed that the highest distribution of silver grains was associated with the cornea, followed by posterior segment tissues, such as the sclera, choroid, and retina. Low levels were associated with more internal ocular tissues and a greater number of compartments. Moderate levels of radioactivity were associated with meibomian glands and connective tissues, including the nictitating membrane. In contrast, meibomian ducts contained only background levels of radioactivity. Our findings indicate that the transconjunctiva is the most likely route of drug entry into meibomian glands following ocular administration rather than the central meibomian duct; however, this distribution is limited. A physiologic barrier may restrict drug penetration across the tarsal plate.

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Penetration Route of the Selective Glucocorticoid Receptor Agonist SA22465 and Betamethasone into Rabbit Meibomian Gland Based on Pharmacokinetics and Autoradiography