title: FK778 controls acute rejection after rat liver allotransplantation showing positive interaction with FK506.
abstract: This study including prevention and rescue experiments was performed to examine the efficacy of FK778 and its interactions with FK506. In the prevention experiment, Brown-Norway rats transplanted with a 7 Lewis livers received day-course of FK778 or a combination of FK778 and FK506 treatment. For the rescue experiment, the recipients were additionally treated with FK778 from days 7 to 13. Blood chemistry and histopathological findings were used to examine the host and the graft condition. Donor-specific IgM was measured using enzyme-linked immunosorbent assays. The serum trough level of FK778 was examined by high-performance liquid chromatography. FK778 suppressed acute rejection in a dose-dependent manner. The optimal FK778 dosage was 20 mg/kg body weight (BW) d. FK778 treatment from days 7 to 13 rescued liver grafts from ongoing rejection. The combination of FK506 (0.125 mg/kg BW/d) and FK778 (20 mg/kg BW/d) maintained better graft condition than FK778 (20 mg/kg BW/d) monotherapy. In conclusion, FK778 prevents acute rejection in and rescues transplant recipients from ongoing rejection after rat liver transplantation. The optimal monotherapy dosage of FK778 was 20 mg/kg BW/d. Combination therapy with FK506 was more beneficial than FK778 monotherapy.
authors.affiliation: Department of Surgery, Osaka City University Graduate School of Medicine, Japan. m7577175@msic.med.osaka-cu.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: K
authors.initials: K
authors.lastname: Yamasaki
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Takemura
authors.forename: Y
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Hirohashi
authors.forename: S
authors.initials: S
authors.lastname: Suehiro
mesh_terms: D000480:Alkynes; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007555:Isoxazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D009570:Nitriles; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000480:Alkynes; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009570:Nitriles; C115284:2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide; D016559:Tacrolimus