title: Tacrolimus (FK506) malabsorption: management with fluconazole coadministration.
abstract: We report the use of fluconazole to control primary immunosuppressive management with tacrolimus in a 9-year-old liver transplant recipient. Progressive increases in the doses of both cyclosporin (up to 20 mg/kg/day) and, subsequently, tacrolimus (up to 60 mg/day) failed to maintain immunosuppressive levels of both agents. After excluding poor compliance, drug interactions and analytical problems and identifying poor bioavailability (< 2.6%) and rapid clearance (4.2 l/h), fluconazole (100 mg/day) was initiated to inhibit tacrolimus metabolism and consistent therapeutic blood levels of tacrolimus were achieved. However, graft function had deteriorated irrevocably and retransplantation was performed. Simultaneous use of tacrolimus (5 mg/day) and fluconazole (100 mg/day) maintained immunosuppression after transplantation. Three weeks later, obstruction of the Roux loop caused deteriorating liver function and tacrolimus blood levels fell. After correction at laparotomy, stabilisation was achieved and discharge was possible on 5 mg tacrolimus b.i.d. plus fluconazole (100 mg).
authors.affiliation: Paediatric Liver Services King's College Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Dhawan
authors.forename: J M
authors.initials: JM
authors.lastname: Tredger
authors.forename: P J
authors.initials: PJ
authors.lastname: North-Lewis
authors.forename: C E
authors.initials: CE
authors.lastname: Gonde
authors.forename: A P
authors.initials: AP
authors.lastname: Mowat
authors.forename: N J
authors.initials: NJ
authors.lastname: Heaton
mesh_terms: D000042:Absorption; D002648:Child; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D015725:Fluconazole; D016559:Tacrolimus