Effectiveness of Sirolimus in Combination with Cyclosporine against Chronic Rejection in a Pediatric Liver Transplant Patient

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  • Shinke Haruka
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Hashi Sachiyo
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Kinoshita Risa
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Taniguchi Risa
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Sugimoto Mitsuhiro
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Matsubara Kazuo
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital
  • Ogawa Eri
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Sonoda Mari
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Takada Narito
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Yoshizawa Atsushi
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Ogawa Kohei
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Okamoto Shinya
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Uemoto Shinji
    Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Hospital
  • Masuda Satohiro
    Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital

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The patient is a 3-year-old boy who received living-donor liver transplantation (LDLT) for hepatoblastoma, with his mother as the donor. Oral tacrolimus was started at a dose of 0.3 mg every 12 h from day 1, with the dosage adjusted on the basis of trough concentrations. The levels of aspartate aminotransferase (AST), alanine transferase (ALT), and total bilirubin (T-bil) were 110 U/L, 182 U/L, and 12.6 mg/dL, respectively, when chronic rejection (CR) was pathologically diagnosed. Then, sirolimus at a dose of 1.0 mg/d was added to the tacrolimus-based regimen. The T-bil level rapidly decreased to 5.4 mg/dL, without changes in AST and ALT. Because the intracellular receptor of sirolimus and tacrolimus is FK506-binding protein 12, we switched tacrolimus to cyclosporine at a dose of 60 mg/d to avoid competitive inhibition between these 2 drugs. The target trough concentration of sirolimus and cyclosporine was set to around 15 ng/mL and 180 ng/mL, respectively. The concentration/dose ratio of sirolimus was significantly correlated with the blood cyclosporine level (r=0.5293, p<0.05), suggesting the pharmacokinetic interaction between these 2 drugs. Thereafter, the levels of AST and ALT as well as the T-bil were successfully decreased to 73 U/L, 83 U/L, and 3.0 mg/dL, respectively. These results suggest that sirolimus therapy in combination with cyclosporine may be an effective treatment against CR after liver transplantation.

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