C2 –C0 VALUES DETERMINATION FOR MONITORING CYCLOSPORINE THERAPHY IN STABLE HEART TRANSPLANTED PATIENTS

Abstract

O340 Aims: The cyclosporine two hours plasmatic level determination (C2) seems to be better related to safety and efficacy of immunosuppressive regimen than throught level (C0) in stable and “the novo” liver and kidney transplanted patients. There are not clear results about the safe and efficacy of C2 level compared to C0 in the immunosuppressive regimen of stable transplanted heart; this study have been performed in stable transplanted heart to determine efficacy and safety of C2 versus C0. Methods: From 01/09/01 to 15/03/04, 1148 samples (574 C0 determination and related C2) were taken to 110 stable and “the novo” heart transplanted patients, orally treated with Neoral micro-emulsioned Cyclosporine (Cya) and monitored with C0 trought levels. From this population, 60 patients with a sufficient number of samples/patient (at least 4) with a mean ratio of 5,2, were studied and divided in two subgroups: Group A, 22 patients with a relatively constant C2 and related AUC values (“costant” defines as +/- 30% in four different samples) and: Group B, 38 patients “inconstant adsorbers”, with great variation (> +/- 30%) of C2 values despite constant given cyclosporine dosage. Cya side effects, acute rejection episodes and chronic graft rejection were observed and related to C2 measured levels. Results: Total number of biopsies was 427; 21 episodes of acute rejection ISHLT grade > IIIA occurred (21/427, 4,9%). There was no statistical difference between number of acute rejection in the two groups. Only 7 rejection episodes occurred in transplanted patients over 1 year; in the others events, there was no difference about immunosuppressive treatment (triple standard : Cya+prednisone+ azathioprine). In the patients free of rejection, mean C2 level observed were: 1500 ng/ml (range 1180-1890) at three months from transplantation, 1200 ng/ml (range 1050-1630) at 6th month, 1000 ng/ml (range 650-1440) at 1 year, 750 ng/ml (range 550-970) at two years. Higher C2 levels were related to increased frequency of Cya side effects: sistemic hypertension (47% group A vs 36% group B), gum hyperplasia (A 21% vs B 9%), hypercolesterolaemia (A 42% vs B 22%), tremors and peripheral paraestesia (A 47% vs B 31%). There were no differences between the two group regard renal disfunction. Conclusions: Despite the small number of patients C2 levels determination appears to be very helpfull when associated to C0 in clinical monitoring of immunosuppression (identification of Cya over-exposed and low-adsorber patient). In heart transplanted patients the recommendable C2 levels appeares to be higher in respect to liver or kidney transplanted patients. Because of an higher dosage of Cya, C2 monitoring alone can be associated to an higher report of side effects than in liver and kidney transplantation.