EVALUATION OF THE DRUG-INTERACTION BETWEEN INTRAVENOUS HIGH-DOSE FLUCONAZOLE AND CYCLOSPORINE OR TACROLIMUS IN BONE-MARROW TRANSPLANT PATIENTS

The purpose of this open-label, prospective study was to compare stead y state concentrations and clearances of intravenously administered cy closporine or tacrolimus with and without concomitant high-dose (400 m g/day) fluconazole in allogeneic BMT patients. Twenty-one patients wer e evaluable. The mean steady state cyclosporine and tacrolimus concent rations without fluconazole were 320.3 and 18.2 ng/ml and increased to 389.2 and 21.2 ng/ml, respectively, after the addition of fluconazole , corresponding to a 21% (P=0.031) and 16% (P=0.125) increase. The mea n steady state clearance of cyclosporine and tacrolimus without flucon azole was 6.82 and 1.28 ml/min/kg, which decreased to 5.57 and 1.10 ml /min/kg with fluconazole, corresponding to a 21% (P=0.031) and 16% (P= 0.125) decrease, respectively. The 21% difference in the cyclosporine concentration and clearance was not thought to be clinically significa nt. These results suggest that fluconazole's interaction with cyclospo rine or tacrolimus may be a result of fluconazole's inhibition of gut metabolism, resulting in a greater extent of absorption.