Ocular penetration of cyclosporin A. The rabbit eye.

In the rabbit, after oral ingestion of 20 mg/kg/day of cyclosporin A (CsA) a high level of the drug is found in the blood. This level increases steadily during the first 3 days, leveling off by days 5-7. Although the blood level of CsA was within the "therapeutic window" of 400-600 ng/ml, the drug was not detected within the ocular tissues. Local application using 2% CsA in olive oil induced a high concentration of the drug in the cornea and conjunctive but no detectable levels within the intraocular structures. When a significant intraocular inflammation is induced in one of the rabbit eyes, CsA ingested orally reaches detectable levels in nearly all tissues of the inflamed eyes. Highest concentrations of the drug were observed within the chorioretinal complex in these eyes. In the contralateral (noninflamed) eyes, however, no detectable CsA was found either intraocularly or extraocularly. In the significantly inflamed eyes, local application of the drug induced a high CsA level within the anterior segment only, without any detectable levels within the choroid and retina.