title: Effectiveness of sirolimus in combination with cyclosporine against chronic rejection in a pediatric liver transplant patient.
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.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto 606–8507, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinke
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Hashi
authors.forename: Risa
authors.initials: R
authors.lastname: Kinoshita
authors.forename: Risa
authors.initials: R
authors.lastname: Taniguchi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
authors.forename: Eri
authors.initials: E
authors.lastname: Ogawa
authors.forename: Mari
authors.initials: M
authors.lastname: Sonoda
authors.forename: Narito
authors.initials: N
authors.lastname: Takada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Okamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
mesh_terms: D002675:Child, Preschool; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus