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A. K. Chappa, J. W. Proksch; Ocular Pharmacokinetics of BOL-303242-X, a Novel Selective Glucocorticoid Receptor Agonist (SEGRA), in Pigmented Rabbits. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2629.
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BOL-303242-X is a Selective Glucocorticoid Receptor Agonist (SEGRA) currently of interest for the treatment of a variety of ocular diseases. The ocular pharmacokinetics of BOL-303242-X have been investigated in pigmented rabbits following single and repeated topical dosing over a wide range of dose levels.
BOL-303242-X was formulated as a suspension and administered topically to pigmented rabbits in a dose volume of 35-50 µL over a dose range of 0.01 to 3000 µg/eye. At predetermined time intervals after dosing, rabbits were euthanized under anesthesia, and the eyes enucleated and dissected with the collection of various ocular tissues and fluids. Levels of BOL-303242-X in collected samples were determined using LC/MS/MS.
BOL-303242-X was rapidly absorbed and widely distributed into ocular tissues after topical ocular administration to pigmented rabbits. In general, BOL-303242-X concentrations were highest in tears followed by conjunctiva and cornea with somewhat lower levels observed in iris/ciliary body and retina. For example, following topical ocular administration of a single 50-µg dose of BOL-303242-X, maximal concentrations in tears, conjunctiva, cornea, iris/ciliary body, retina, and aqueous humor were 982 µg/g, 7.68 µg/g, 1.05 µg/g, 0.0143 µg/g, 0.0129 µg/g, and 0.000328 µg/mL, respectively. Over the wide range of doses studied, BOL-303242-X concentrations in ocular tissues generally increased with increasing dose levels; however, the increase in exposure tended to be less than proportional to the increase in the administered dose. In studies involving repeated administration of BOL-303242-X, ocular exposure tended to be higher following 4x/day dosing compared with a single administration. Systemic exposure to BOL-303242-X following topical ocular dosing was generally low, with an average maximum concentration less than 0.2 ng/mL at a dose of 50 µg/eye.
BOL-303242-X is rapidly absorbed into target ocular tissues after topical ocular administration with minimal systemic exposure. The promising pharmacokinetic behavior of BOL-303242-X, together with its potent anti-inflammatory and immunomodulatory properties supports the ongoing clinical development of this compound.
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