Adding sirolimus to tacrolimus-based immunosuppression in pediatric renal transplant recipients reduces tacrolimus exposure.
In adult renal recipients, coadministration of tacrolimus (TAC) and sirolimus (SIR) results in reduced exposure to TAC at SIR doses of 2 mg/day. Eight pediatric renal recipients (median age at transplant 2.0 years, range: 1.2-12.9 years) were converted to TAC- and SIR-based immunosuppression as a rescue therapy. All patients had biopsy-proven chronic allograft nephropathy. TAC levels were measured using a commercially available EMIT assay and SIR levels with a newly developed assay based on the LC-MS MS technology. SIR was started at 0.13+/-0.05 mg/kg/day (3.51+/-1.26 mg/m2/day) in two divided doses. TAC was given at 0.14+/-0.09 mg/kg/day, resulting in a trough level of 6.3+/-2.5 ng/mL. After the addition of SIR, the median dose required to keep TAC blood trough concentrations within the target range increased by 71.2% (range: 21.9-245.4%), dose-normalized TAC exposure (AUC) decreased to 67.1% and the dose-normalized C(max), a surrogate for absorption rate, to 53.8% (both geometric means) while terminal half-life (t1/2), a pharmacokinetic parameter characterizing systemic elimination, remained unchanged (p<0.93). Adding SIR to TAC-based immunosuppression in young pediatric renal transplant recipients results in a significant decrease of TAC exposure. TAC trough levels should be monitored frequently.
Department of Pediatrics, Division of Pediatric Nephrology, Children's Hospital of Easter Ontario, University of Ottawa, Ontario, Canada. filler@cheo.on.ca
Guido
G
Filler
Taiwo
T
Womiloju
Janusz
J
Feber
Nathalie
N
Lepage
Uwe
U
Christians
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007223:Infant; D007676:Kidney Failure, Chronic / Q000097:blood / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D012189:Retrospective Studies; D020123:Sirolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus