CYCLOSPORINE-A AND ITS METABOLITES IN THE ANTERIOR-CHAMBER AFTER TOPICAL AND SYSTEMIC APPLICATION AS DETERMINED WITH HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ELECTROSPRAY MASS-SPECTROMETRY

Penetration of ciclosporin A (CSA) into the anterior chamber through t he intact cornea after topical application is difficult due to its hyd rophobic structure. Following systemic application the anterior-chambe r levels of CSA are reported to be higher. CSA metabolites are more hy drophilic than CSA. Only high-performance liquid chromatography-electr ospray 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 d rops preceding routine cataract surgery with 2 different application s chemes and in 7 patients receiving systemic CSA after high-risk penetr ating keratoplasty. After topical application the average CSA level me asured in the anterior chamber was 81 ng/ml. The CSA-metabolite levels were much higher, reaching an average of 378 ng/ml. After systemic th erapy the anterior-chamber levels of CSA and of the metabolites were m uch more balanced at 256 and 317 ng/ml, respectively. CSA penetrates i nto 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 concentra tions than is CSA, and the metabolite pattern differs from that seen a fter systemic therapy. The relevance of these findings to the immunosu pressive activity of the CSA metabolites, however, remains unclear.