Journal
PEDIATRIC TRANSPLANTATION
Volume 8, Issue 2, Pages 171-177Publisher
BLACKWELL MUNKSGAARD
DOI: 10.1046/j.1399-3046.2003.00148.x
Keywords
sirolimus; pharmacokinetics; children; kidney transplantation; half-life; mycophenolate mofetil
Categories
Funding
- NCRR NIH HHS [M01 RR002172, M01 RR000240, M01 RR02172, K23 RR016080, K23 RR16080, RR00240] Funding Source: Medline
- NIAID NIH HHS [U01-AI46135] Funding Source: Medline
Ask authors/readers for more resources
Immunosuppression with SRL may provide an opportunity to avoid long-term exposure to the nephrotoxicity of CNI. Thus, we have initiated an experimental protocol of IL-2r antibody induction, prednisone, MMF and SRL in pediatric renal transplant recipients (median age 15.5 yr, IQR 8.5, range 1.3-21.7). The recipients were treated with daclizumab every 2 wk for the first 2 months, prednisone on a tapering schedule, MMF at 1200 mg/m(2)/day and SRL given b.i.d. The SRL was dosed to achieve defined target whole blood 12-h trough levels. We performed 24 SRL PK profiles in 13 stable pediatric renal transplant recipients at 1 and 3 months post-transplant. Half-life (T-1/2) and terminal T-1/2 were 9.7 (7.1-24.6) and 10.8 (4.4-95.2) hours (median, range) respectively at month 1, and were 9.6 (5-17.8) and 12.1 (4.7-71.0) hours respectively at month 3. SRL trough levels correlated with AUC (r(2) = 0.84, p < 0.001). There was no relationship between SRL and mycophenolic acid (MPA) AUC values (r(2) = 0.04). During the first 3 months post-transplant only one patient experienced severe neutropenia and another patient had subclinical (histologic) evidence of a mild acute rejection episode with no change in renal function. We conclude that the T-1/2 of SRL in pediatric renal transplant recipients not treated with CNI is much shorter than what has been reported for adults, due to rapid metabolism. We conclude that children require SRL dosing every 12 h, higher doses and frequent drug monitoring to achieve target SRL concentrations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available