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  • Title: Cyclosporin-A and its metabolites in the anterior chamber after topical and systemic application as determined with high-performance liquid chromatography-electrospray mass spectrometry.
    Author: Althaus C, Dagres E, Reinhard T, Christians U, Sundmacher R.
    Journal: Ger J Ophthalmol; 1996 Jul; 5(4):189-94. PubMed ID: 8854101.
    Abstract:
    Penetration of cyclosporin A (CSA) into the anterior chamber through the intact cornea after topical application is difficult due to its hydrophobic structure. Following systemic application the anterior-chamber levels of CSA are reported to be higher. CSA metabolites are more hydrophilic than CSA. Only high-performance liquid chromatography-electrospray mass spectrometry allows exact quantification of the CSA level and the identification of all CSA metabolites. We studied the anterior-chamber levels of CSA and different CSA metabolites after topical and systemic application. CSA and CSA-metabolite anterior-chamber levels were measured in 49 patients after topical application of CSA 2% eye drops preceding routine cataract surgery with 2 different application schemes and in 7 patients receiving systemic CSA after high-risk penetrating keratoplasty. After topical application the average CSA level measured in the anterior chamber was 81 ng/ml. The CSA-metabolite levels were much higher, reaching an average of 378 ng/ml. After systemic therapy the anterior-chamber levels of CSA and of the metabolites were much more balanced at 256 and 317 ng/ml, respectively. CSA penetrates into the anterior chamber after topical eye-drop application, but these levels are much lower than those measured after systemic CSA therapy. After topical application the CSA metabolites might play an important role; they are found in the anterior chamber in much higher concentrations than is CSA, and the metabolite pattern differs from that seen after systemic therapy. The relevance of these findings to the immunosuppressive activity of the CSA metabolites, however, remains unclear.
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