| 7 | Post-dose 12-hour trough concentration of mycophenolate mofetil co-administrated with cyclosporine in dog显示文摘Mycophenolate mofetil (MMF) is a pro-drug for mycophenolic acid (MPA) which reduces the likelihood of allograft rejection after renal transplantation. It was known that post-dose 12-hour trough concentration of MMF will be influenced by several factors including renal function and cyclosporine (CsA) co-administration and need adjustment when used in clinical renal transplanted patients,but there is still few data in dog. The objective of this study is to investigate Post-dose 12-hour trough concentration and determine the optimal dose of MMF in renal transplanted dog. Study 1: Investigate the relationship between oral dose and Post-dose 12-hour trough concentration of MPA in healthy dogs. Study 2: Investigate the changes of post-dose 12-hour trough concentration of MPA in healthy dogs when co-administrating with CsA. Study 3: Investigate the relationship between dose and Post-dose 12-hour trough concentration of MPA in low glomerular filtration rate (GFR) model dogs with CsA co-administration. 8 Adult female beagle dogs aged 1-2 years old,weight in 1. 5-13. 5kg. Study 1: After 7 days of prier oral administration of MMF (10 mg/kg,n = 4; 30 mg/kg,n = 4),MMF was oral administrated in the same dose in day 8,and MPA blood concentrations were measured at 0,20,40,60,90,120, 240,360,480,and 720 min after oral dose. Study 2: After 7 days of prier administration of 10 mg/kg MMF with (n = 4) or without (n = 4) 10 mg/kg CsA,MMF was oral administrated in the same dose with or without CsA in day 8,and post-dose 12-hour trough concentrations were measured. Study 3: Low GFR model dogs were prepared with renal artery ligation before this study. After 7 days of prier co-administration of 10 mg/kg (n = 4) or 20 mg/kg (n = 4) MMF with 10 mg/kg CsA,MMF was oral administrated in the same dose in day 8 and 12-hour trough concentrations of MPA were measured. MPA concentrations were measured by high performance liquid chromatography method. 12-hour trough concentrations of MPA of healthy dogs were 1313 ± 222 ng/mL (10 mg/kg) and 2117 ± 545 ng/mL (30 mg/kg),and 2 dogs of 30 mg/kg group show GI disturbance during study period. 12-hour trough concentrations of MPA of healthy dogs co-administrated with CsA were lower than thus without CsA co-administrated (P < 0. 05). 12-hour trough concentrations of MPA of low GFR model dogs with CsA co-administration were 416 ± 202 ng/mL (10 mg/kg) and 815 ± 229 ng/mL (30 mg/kg). 12-hour trough concentrations of MPA of healthy dogs were measured. Higher oral dose (30 mg/kg) can reach higher blood level but may also associate with GI disturbance. When co-administrated with CsA,MPA blood level will decrease even in dogs with lower GFR. It will be necessary to adjust the dose to maintain the trough concentrations of MPA when co-administrate with Cyclosporine. Although MPA is reported to show excellent immunosuppressant effects to reduce the likelihood of allograft rejection in human medicine,there is still few data about the dosage and trough concentrations in veterinary medicine. This investigation provides useful information to make immunosuppressant protocol use MPA (MMF) only or MPA (MMF) in combination with CsA in dog. | Yijyun Li Zheng Cao Akiyoshi Hayashi Keichiro Mie Maki Ishibashi | 2012 | 畜牧与兽医2012，44，S2： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员