title: An open-label, concentration-ranging trial of FK506 in primary kidney transplantation: a report of the United States Multicenter FK506 Kidney Transplant Group.
abstract: This was a multicenter, open-label, concentration-ranging trial of FK506 and cyclosporine in 120 patients undergoing primary cadaveric kidney 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 blood 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, necessitating 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 rejection was significantly lower (14% for FK506 and 32% for cyclosporine; P=0.048) for the aggregate of all FK506-treated patients versus cyclosporine. The incidence of neurotoxic and gastrointestinal events was higher among FK506-treated patients during the first month after transplant. A significant trend was observed for increasing toxicity with increasing maximum trough FK506 concentrations (P=0.01) and for decreasing rates of rejection with increasing minimum trough FK506 concentrations (P=0.021). FK506 was effective in preventing early rejection in kidney transplant recipients. The target range of whole blood levels that optimizes efficacy and minimizes toxicity seems to be 5-15 ng/ml. The corresponding recommended initial dose of FK506 for kidney transplant recipients seems to be 0.2 mg/kg/day.
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, 35294, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Laskow
authors.forename: F
authors.initials: F
authors.lastname: Vincenti
authors.forename: J F
authors.initials: JF
authors.lastname: Neylan
authors.forename: R
authors.initials: R
authors.lastname: Mendez
authors.forename: A J
authors.initials: AJ
authors.lastname: Matas
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus