AN OPEN-LABEL, CONCENTRATION-RANGING TRIAL OF FK506 IN PRIMARY KIDNEY-TRANSPLANTATION - A REPORT OF THE UNITED-STATES MULTICENTER FK506 KIDNEY-TRANSPLANT GROUP

This was a multicenter, open-label, concentration-ranging trial of FK5 06 and cyclosporine in 120 patients undergoing primary cadaveric kidne y transplant, Patients were randomized to a cyclosporine-based regimen or to one of three FK506-based regimens designed to achieve low (5-14 ng/ml), medium (15-25 ng/ml), or high (26-40 ng/ml) trough whole bloo d levels, Corresponding initial doses of FK506 were 0.2, 0.3, and 0.4 mg/kg/day, Patients were evaluated at 42 days after transplant for the occurrence of the first episode of acute rejection or toxicity, neces sitating a dosage reduction, There was no significant difference among the three FK506-based regimens and the cyclosporine-based regimen for rejection or toxicity at 42 days, However, the incidence of acute rej ection was significantly lower (14% for FK506 and 32% for cyclosporine ; P=0.048) for the aggregate of all FK506-treated patients versus cycl osporine. The incidence of neurotoxic and gastrointestinal events was higher among FK506-treated patients during the first month after trans plant, A significant trend was observed for increasing toxicity with i ncreasing maximum trough FK506 concentrations (P=0.01) and for decreas ing rates of rejection with increasing minimum trough FK506 concentrat ions (P=0.021). FK506 was effective in preventing early rejection in k idney transplant recipients, The target range of whole blood levels th at optimizes efficacy and minimizes toxicity seems to be 5-15 ng/ml. T he corresponding recommended initial dose of FK506 for kidney transpla nt recipients seems to be 0.2 mg/kg/day.