Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co-therapy

被引:30
|
作者
Schachter, Asher D.
Benfield, Mark R.
Wyatt, Robert J.
Grimm, Paul C.
Fennell, Robert S.
Herrin, John T.
Lirenman, David S.
McDonald, Ruth A.
Munoz-Arizpe, Ricardo
Harmon, William E.
机构
[1] Childrens Hosp, Div Nephrol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Childrens Hosp, Harvard MIT Hlth Sci & Technol, Informat Program, Boston, MA 02115 USA
[4] Univ Alabama, Div Pediat Nephrol, Birmingham, AL USA
[5] Lebonheur Childrens Hosp & Med Ctr, Childrens Fdn Res Ctr, Memphis, TN USA
[6] Univ Calif San Diego, Dept Pediat, Div Pediat Nephrol, La Jolla, CA 92093 USA
[7] Univ Florida, Dept Pediat, Div Nephrol, Gainesville, FL USA
[8] British Columbia Childrens Hosp, Div Nephrol, Vancouver, BC V6H 3V4, Canada
[9] Univ Washington, Childrens Hosp & Reg Med Ctr, Div Nephrol, Seattle, WA 98195 USA
[10] Hosp Infantil Mexico Dr Federico Gomez, Dept Nefrol, Mexico City, DF, Mexico
关键词
sirolimus; pharmacokinetics; calcineurin inhibitors; cyclosporine; tacrolimus; children; kidney transplantation;
D O I
10.1111/j.1399-3046.2006.00541.x
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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.
引用
收藏
页码:914 / 919
页数:6
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