title: Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co-therapy.
abstract: 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.
authors.affiliation: Division of Nephrology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. asher.schachter@childrens.harvard.edu
authors.forename: Asher D
authors.initials: AD
authors.lastname: Schachter
authors.forename: Mark R
authors.initials: MR
authors.lastname: Benfield
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wyatt
authors.forename: Paul C
authors.initials: PC
authors.lastname: Grimm
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fennell
authors.forename: John T
authors.initials: JT
authors.lastname: Herrin
authors.forename: David S
authors.initials: DS
authors.lastname: Lirenman
authors.forename: Ruth A
authors.initials: RA
authors.lastname: McDonald
authors.forename: Ricardo
authors.initials: R
authors.lastname: Munoz-Arizpe
authors.forename: William E
authors.initials: WE
authors.lastname: Harmon
mesh_terms: 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*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus