Distribution of cyclosporin A in the cornea after topical or oral administration.

The purpose of this study was to determine levels of cyclosporin A (CsA) in ocular tissues and fluids after oral or topical administration of CsA in humans requiring immunosuppression for penetrating keratoplasty and to evaluate the sensitivity of a high performance liquid chromatography coupled to electrospray mass spectrometry (LC-MS). High-risk penetrating keratoplasty was performed on 11 patients requiring 5 mg/kg of oral cyclosporin A and 9 patients with topical 0.5% (suspension, equivalent to 5 mg/ml)) preoperative immune suppression. Venous blood samples, as well as aqueous samples, were obtained for some patients, and the central 6.0-8.5 mm corneal buttons were removed and dissected into cornea epithelium, stroma and endothelium and analyzed for CsA levels by LC-MS. The mean values (concentration) of the specimens analyzed (obtained from 11 patients on oral CsA) showed 2.45 +/- 2.12 and 0.35 +/- 0.49 ng CsA/mg tissue in the epithelium and endothelium, respectively. A much smaller concentration, 0.13 +/- 0.14 ng CsA/mg tissue was observed in the stroma. There was a fair amount of CsA in the serum at the time of surgery but no detectable CsA in all aqueous humor samples analyzed. In cases of topical application, the mean concentration of CsA was similarly highest in the epithelium, 64.29 +/- 39.92 ng CsA/mg tissue, followed by the endothelium, 9.98 +/- 6.55 ng CsA/mg tissue, with the lowest levels found in the stroma. Topical application of CsA is able to achieve high levels of CsA in the corneal epithelium, higher than that achieved from oral administration of CsA.