Yamamoto S, Okuda T, Yamasaki K, Tanaka H, Takemura S, Minamiyama Y, Ikeda K, Hirohashi K, Suehiro S
Department of Surgery, Osaka City University Graduate School of Medicine, Japan.
Transplant Proc. 2005 Jan-Feb;37(1):126-9. doi: 10.1016/j.transproceed.2005.02.016.
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.
本研究包括预防和救援实验，旨在检验FK778的疗效及其与FK506的相互作用。在预防实验中，移植了7个Lewis肝脏的Brown-Norway大鼠接受了为期一天的FK778治疗或FK778与FK506联合治疗。在救援实验中，受体在第7天至第13天额外接受FK778治疗。通过血液化学和组织病理学检查来评估宿主和移植物的状况。使用酶联免疫吸附测定法测量供体特异性IgM。通过高效液相色谱法检测FK778的血清谷浓度。FK778以剂量依赖的方式抑制急性排斥反应。FK778的最佳剂量为20mg/kg体重（BW）/天。在第7天至第13天给予FK778治疗可使肝移植物从正在进行的排斥反应中获救。FK506（0.125mg/kg BW/天）与FK778（20mg/kg BW/天）联合使用比FK778（20mg/kg BW/天）单药治疗能更好地维持移植物状况。总之，FK778可预防大鼠肝移植后的急性排斥反应，并使移植受体从正在进行的排斥反应中获救。FK778的最佳单药治疗剂量为20mg/kg BW/天。与FK506联合治疗比FK778单药治疗更有益。
