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T. Tajika, A. Isowaki, T. Ogawa, A. Pongpeerapat, J. Shudo, M. Yamaji, T. Kamakura, T. Matsubara; Ocular Pharmacokinetic Study After Transdermal Application of 14C-Ketotifen Patch to Lower Eyelid of Rabbits. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6329.
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The transdermal patch containing ketotifen is currently being developed for the treatment of allergic conjunctivitis. This patch is applied on the eyelid expecting to deliver the drug continuously to the conjunctiva. The ocular pharmacokinetic study was conducted to evaluate the radioactivity distribution after applying the 14C-ketotifen patches on the lower eyelid of the rabbits.
14C-Ketotifen patches were applied to the left lower eyelids of New Zealand White rabbits for 8 hrs. The radioactivity concentrations in the ocular tissues of both eyes were measured at 2, 4, 8, 9, 12, 16, 24, 72 and 168 hrs after transdermal application. The pharmacokinetic parameters were calculated from the radioactivity concentrations with non-compartment model.
The radioactivity concentrations in most of ocular tissues in the applied eyes reached a peak at 8 hrs. The maximum radioactivity concentration (Cmax) in the lower eyelid was the highest (44,621 ng eq./g) in all tissues, followed by the lower conjunctiva (140), upper eyelid (67), upper conjunctiva (31), tear, posterior sclera, cornea and anterior retina/choroid. The half-life (t1/2) of the lower eyelid, lower conjunctiva, upper eyelid, and upper conjunctiva was 62, 45, 92 and 23 hrs, respectively. The Cmax and t1/2 of ketotifen in the plasma was 7.6 ng eq./mL and 12 hrs, respectively. The Cmax of ocular tissues in the non-applied eyes were 2 times less than that of the plasma and very low compared to those in the applied eyes.
These results indicate that the lower eyelid may act as a reservoir for the drug and ketotifen was continuously transferred from the lower eyelid to the conjunctiva. The t1/2 in the conjunctiva suggests that the application of ketotifen patch for 8 hrs might be an effective treatment of allergic conjunctivitis for at least 1 day.
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