Τόμος 3 (1985) – Τεύχος 4 – Άρθρο 2 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 3 (1985) – Issue 4 – Article 2 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Cyclosporin–A

ALKIS KOSTAKIS

^{Β’ Προπαιδευτική Χειρουργική Κλινική Πανεπιστημίου Αθηνών}

3: 174-184 (1985)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

3: 174-184 (1985)

Cyclosporin–A

Cyclospοrin-Α is a powerful immunossupressant which was isolated by Sandoz Laboratories in 1972. It was extracted from the soil fungi Trichoderma polysporum Rifai and Cycindrocarpum Lucidum. It is a lipo­phylic cyclic peptide of 11 amino acids and has molecular weight of 1200 daltons. Following oral administration, absorption of cyclosporin from the gastrointestinal tract occurs with a half-life of about one hour and the fat contains the highest tissue concentration, as expected from the high lipophilicity of cyclosporin. Its distribution between plasma and blood cells depends on temperature. Metabolism of cyclo­sporin is mainly mediated through the P-450 hepatic enzyme. The major route of elimination of cyclosporin and its metabolites is biliary excretion. A number of drugs have been report­ed to interact with cyclosporin, these intera­ctions resulting in either an increase or de­crease in blood cyclosporin concentration. Two methods are available for the assay of cyclo­sporin concentrations in blood, radioimmunoas­say (RIA) and high-performance liquid chroma­tography (HPLC). The mainly used is the first one and the recommended therapeutic range of steady-state through this method in whole blood is 300 to 800 ng/ml. The main action of cyclosporin is selective against the T-lymphocy­tes, while it has little effect on 13 cells per se. A great deal of information has accumulated over the first years about the immunosuppressive potency of this drug in various models of tissue transplantation in several species and the clini­cal results achieved with this agent indicate that it has an important part to play in future immunosuppressive regimes for organ trans­plantation. Although present data suggest that immunosuppressive and nephrotoxic effects are closely correlated, careful chemical dissection of the differential immunosuppressive and toxic activities of cyclosporine’s metabolites may af­ford new approaches to improve the therapeu­tic window for effective cyclosporin use.

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