FK778 controls acute rejection after rat liver allotransplantation showing positive interaction with FK506.
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.
Yamamoto
S
S
Department of Surgery, Osaka City University Graduate School of Medicine, Japan. m7577175@msic.med.osaka-cu.ac.jp
Okuda
T
T
Yamasaki
K
K
Tanaka
H
H
Takemura
S
S
Minamiyama
Y
Y
Ikeda
K
K
Hirohashi
K
K
Suehiro
S
S
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
D000480:Alkynes; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D009570:Nitriles; C115284:2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide; D016559:Tacrolimus