Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co-therapy.
We have previously reported sirolimus (SRL) pharmacokinetics (PK) in pediatric renal transplant recipients on a calcineurin inhibitor (CNI)-free protocol. We now report pediatric SRL PK in pediatric renal transplant patients receiving SRL + CNI. SRL was dosed to achieve target trough levels between 10 and 20 ng/mL. We performed 49 SRL PK profiles in pediatric renal transplant recipients receiving SRL in combination with either cyclosporine (CsA; 25 profiles), or tacrolimus (TCL; 24 profiles). Ten of the SRL + TCL profiles were obtained from children receiving SRL on a b.i.d. dosing regimen. All other SRL profiles were q.d. regimens. We calculated, the maximum concentration (C(max)), AUC, apparent clearance (aCL; dose/AUC) for dose in mg/m(2), and mean residence time (MRT). SRL levels were measured at 6 and 7 time points for b.i.d. and q.d. dosing, respectively. Regression analysis of SRL trough values vs. AUC showed good correlation in the SRL q.d. + CsA, SRL q.d. + TCL, and SRL b.i.d. + TCL groups (r(2) = 0.95, 0.68, and 0.44, respectively). SRL aCL corrected for body surface area was higher in children aged 0-5 yr receiving SRL with either CsA or TCL. SRL dosing schedule should be tailored to each patient. Higher SRL aCL may be present in younger children when administered with CNI.
Schachter
Asher D
AD
Division of Nephrology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. asher.schachter@childrens.harvard.edu
Benfield
Mark R
MR
Wyatt
Robert J
RJ
Grimm
Paul C
PC
Fennell
Robert S
RS
Herrin
John T
JT
Lirenman
David S
DS
McDonald
Ruth A
RA
Munoz-Arizpe
Ricardo
R
Harmon
William E
WE
D000293:Adolescent; D019540:Area Under Curve; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D016030:Kidney Transplantation; D020123:Sirolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus