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Morten Praestegaard, Fraser Steele, Frédéríc Gomez; Pharmacokinetic characterization of a novel ocular formulation of ciclosporin. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5388.
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© ARVO (1962-2015); The Authors (2016-present)
MC2 Biotek is developing PADciclo™, a new and optimized formulation of ciclosporin (CsA) currently in clinical trial for the treatment of moderate to severe dry eye. This new formulation contains less surfactants and is aimed to improve tolerability of ciclosporin formulations for dry eye. In these experiments, the ocular pharmacokinetic properties of the PADciclo™ formulation were evaluated following single and multiple topical administration.
PADciclo™ targets ocular inflammation which is well-known as one of the underlying cause of dry eye and is administered as eyedrops. In the multiple topical administration study, pigmented rabbits received one or two daily unilateral doses (30 µl) of the tested formulations (0.06% (QD and BID) and 0.1% (QD and BID) and Restasis® as a comparator) over ten days. Cmin and C(0.33h) were determined to assess corneal and conjunctival PK of topical CsA at steady state. Systemic absorption was also evaluated.
This is the first report of pharmacokinetic study results of PADciclo™, a novel formulation of ciclosporin administered in eye drops. Following multiple topical administration, based on AUC, the penetration of CsA in conjunctiva and cornea was up to 4 to 5 times higher with PADciclo™ than Restasis®. No CsA was quantified in whole blood for all tested compounds (<LLOQ=0.25ng/mL) showing that systemic absorption is negligible. Following a single topical administration PADciclo™ formulations demonstrated corneal concentrations of CsA that are 4.7-8.4 times higher than Restasis®, and clearance half-lifes that are comparable to Restasis®. No CsA was detected in aqueous humor from any rabbits, regardless of treatment. This study showed that with a single topical administration of PAD formulations, relevant CsA levels were maintained for at least 24 hours.
These pharmacokinetic results showed that PADciclo™ has a superior profile compared to Restasis® with higher penetration of the drug into the cornea and conjunctiva. PADciclo™ appears safe with negligible systemic exposure. These attributes should enable once daily administration in humans at a lower dose compared to Restasis® (0.05% CsA twice a day).
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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