A LOGISTIC-REGRESSION MODEL PROVIDES NOVEL GUIDELINES TO MAXIMIZE THEANTI-ACUTE REJECTION PROPERTIES OF CYCLOSPORINE WITH A MINIMUM OF TOXICITY

Although cyclosporine has become the mainstay of immunosuppression in organ transplantation, there is still no consensus on the criteria to optimize its antirejection activity with minimum toxicity. A clear and objective definition of target cyclosporine trough levels at differen t times from renal transplantation is still lacking, primarily because of the lack of a model correlating cyclosporine levels with probabili ty of rejection or toxicity, In this study, logistic-regression model was developed that was applied to data collected retrospectively from two postoperative periods, i.e., Days 0 to 9 and 10 to 30, in 135 cons ecutive cadaveric renal transplant recipients, for a total of 1851 det erminations, Only minimum and maximum trough levels were considered fo r each period. Concentration-response curves were estimated for Days 0 to 9 (P = 0.0001 for efficacy and P = 0.028 for toxicity) and for Day s 10 to 30 (P = 0.015 for efficacy and P = 0.037 for toxicity), Therap eutic intervals of 330 to 430 ng/mL (parent compound in whole blood) f or Days 0 to 9 and 260 to 390 ng/mL for Days 10 to 30 predicted an inc idence of acute rejection of 22% and 12%, respectively, with a reasona bly low toxicity that primarily consisted of elevation of serum aminot ransferases.