KINETICS OF DEGRADATION OF CYCLOSPORINE-A IN ACIDIC AQUEOUS-SOLUTION AND ITS IMPLICATION IN ITS ORAL ABSORPTION

The kinetics of degradation of cyclosporin A was studied in aqueous solution at 37 and 60-degrees-C over the pH range 0.1-4.0. The predominant degradation reaction at pH < 2 was an isomerization or N,O-acyl rearrangement with formation of isocyclosporin A. A specific acid-catalyzed reaction dominated at pH < 0.5 whereas a spontaneous or water-catalyzed reaction contributed at higher pH values. Half-lives for the degradation were 63 and 79 h at pH 1.1 and 3.0, respectively, and at 37-degrees-C. It is concluded that intragastric degradation is of very minor importance for the absorption of cyclosporin A upon peroral administration.