Effectiveness of sirolimus in combination with cyclosporine against chronic rejection in a pediatric liver transplant patient

Haruka Shinke, Sachiyo Hashi, Risa Kinoshita, Risa Taniguchi, Mitsuhiro Sugimoto, Kazuo Matsubara, Eri Ogawa, Mari Sonoda, Narito Takada, Atsushi Yoshizawa, Kohei Ogawa, Shinya Okamoto, Shinji Uemoto, Satohiro Masuda

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Abstract

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.

Original languageEnglish
Pages (from-to)1221-1225
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume36
Issue number7
DOIs
Publication statusPublished - Jul 1 2013

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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