Pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on mycophenolate mofetil comedication.
BACKGROUND
The aim of this substudy within a prospective, multicenter, placebo-controlled trial was to assess the pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on comedication with mycophenolate mofetil (MMF).


METHODS
Eighty-two patients aged 3 to 18 years, receiving cyclosporine microemulsion, MMF, corticosteroids, and basiliximab or placebo were investigated. Basiliximab serum concentrations were determined by ELISA, CD25+, and CD122+ T lymphocytes by flow cytometry.


RESULTS
Basiliximab clearance adjusted to body surface area was significantly (P<0.05) greater in children versus adults, but the relatively higher basiliximab dose given to children yielded similar exposure compared with adolescents. A cross-study comparison revealed that MMF reduced basiliximab clearance and prolonged CD25 saturation duration from approximately 5 weeks in the absence of MMF to 10 weeks in the presence of MMF. Basiliximab led to a marked reduction of CD25+ T-cell fraction during the first 8 to 10 weeks posttransplant, but did not specifically affect CD122+ T cells. The majority of biopsy-proven acute rejection episodes (BPAR) were observed after interleukin (IL) 2-R desaturation, whereas about a quarter of BPARs occurred despite adequate IL2-R blockade.


CONCLUSIONS
The currently recommended basiliximab dose for pediatric patients, when used with cyclosporine microemulsion and corticosteroids, yielded adequate drug exposure in children and adolescents also under MMF comedication. The observation that about a quarter of BPARs occurred despite adequate IL2-R blockade suggests that another T-cell activation pathway independent of the IL-2/IL-2R pathway is operative, for example, the IL-15 signaling pathway.
Höcker
Britta
B
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.
Kovarik
John M
JM
Daniel
Volker
V
Opelz
Gerhard
G
Fehrenbach
Henry
H
Holder
Martin
M
Hoppe
Bernd
B
Hoyer
Peter
P
Jungraithmayr
Therese C
TC
Köpf-Shakib
Sabine
S
Laube
Guido F
GF
Müller-Wiefel
Dirk E
DE
Offner
Gisela
G
Plank
Christian
C
Schröder
Monika
M
Weber
Lutz T
LT
Zimmerhackl
Lothar B
LB
Tönshoff
Burkhard
B
D000293:Adolescent; D000375:Aging / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics*; D000077552:Basiliximab; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000493:pharmacokinetics; D019409:Interleukin-15 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000276:immunology / Q000493:pharmacokinetics; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000493:pharmacokinetics*; D015398:Signal Transduction / Q000502:physiology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D009173:Mycophenolic Acid