title: FK506 conversion for intractable rejection of the liver allograft.
abstract: Twenty-seven liver transplant recipients with intractable, biopsy-proven, acute or chronic rejection (defined as vanishing bile duct syndrome) were converted from cyclosporin to FK506. Successful conversion was achieved in 9 of 15 patients with acute rejection and in 6 of 12 patients with vanishing bile duct syndrome. A normal bilirubin was achieved more quickly in those with acute rejection (within 1 month) than in those with chronic rejection (within 3 months). A preconversion total bilirubin of less than 12 mg/dl was considered significant with regard to a successful outcome (P = 0.002). Graft survival was 66.7% and patient survival 73% in the case of acute rejection, and 50% and 66.7%, respectively, in the case of chronic rejection. Nephrotoxicity, neurotoxicity, and gastrointestinal side effects were the most serious complications of FK506 conversion. Six of ten patients had a drop in GFR that was 50% or greater after a minimum of 1 month of FK506 exposure. The mean maintenance dose of FK506 to maintain FK506 serum levels of 0.5-1.5 ng/ml was 0.07 mg/kg per 12 h for adults (half the recommended dose), compared to 0.15 mg/kg per 12 h for pediatric patients. This study demonstrates that FK506 can be used successfully to convert patients with intractable acute and chronic rejection. Careful adjustments of FK506 dosages and levels are required to minimize side effects.
authors.affiliation: Department of Pediatrics, University of California at Los Angeles Medical Center 90024-1752.
authors.forename: S V
authors.initials: SV
authors.lastname: McDiarmid
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: R W
authors.initials: RW
authors.lastname: Busuttil
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007275:Injections, Intravenous; D016031:Liver Transplantation / Q000276:immunology*; D016879:Salvage Therapy; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D016572:Cyclosporine; D001663:Bilirubin; D016559:Tacrolimus