BIOEQUIVALENCE OF SOFT GELATIN CAPSULES AND ORAL SOLUTION OF A NEW CYCLOSPORINE FORMULATION

Study Objective. To compare the bioavailability of cyclosporine from t wo oral dosage forms of a new microemulsion formulation. Design. Open, randomized, three-treatment, three-period crossover investigation. Se tting. University-affiliated clinical pharmacology research unit. Pati ents. Twenty-four healthy male volunteers. Interventions. Single oral administrations of cyclosporine 180 mg given as a soft gelatin capsule (reference), an oral solution under fasting conditions, and the oral solution mixed with orange juice. Measurements and Main Results. Seria l venous blood samples were obtained over 48 hours after each administ ration to measure cyclosporine in whole blood by a specific monoclonal radioimmunoassay. For all three treatments, the mean maximum blood co ncentration (C(max)) of approximately 1100 ng/ml was reached at about 1.3 hours (t(max)) after administration; the area under the blood conc entration-time curve (AUC) was, on average, 4700 ng-hr/ml. Bioequivale nce was conclusively demonstrated for both the absorption rate (C(max) and t(max)) and extent (AUC) of cyclosporine among the treatments ina smuch as the point estimates and 90% confidence intervals were within the respective equivalence ranges. Conclusions. When administered in c onjunction with routine concentration monitoring, the two oral dosage forms of the new microemulsion formulation of cyclosporine can be inte rchanged without need for dosage adjustments. In addition, the oral so lution can be mixed with fruit juice without affecting the rate or ext ent of cyclosporine absorption.