title: Pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on mycophenolate mofetil comedication.
abstract: 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.
authors.affiliation: Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Höcker
authors.forename: John M
authors.initials: JM
authors.lastname: Kovarik
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Henry
authors.initials: H
authors.lastname: Fehrenbach
authors.forename: Martin
authors.initials: M
authors.lastname: Holder
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoppe
authors.forename: Peter
authors.initials: P
authors.lastname: Hoyer
authors.forename: Therese C
authors.initials: TC
authors.lastname: Jungraithmayr
authors.forename: Sabine
authors.initials: S
authors.lastname: Köpf-Shakib
authors.forename: Guido F
authors.initials: GF
authors.lastname: Laube
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Müller-Wiefel
authors.forename: Gisela
authors.initials: G
authors.lastname: Offner
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Monika
authors.initials: M
authors.lastname: Schröder
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.forename: Lothar B
authors.initials: LB
authors.lastname: Zimmerhackl
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
mesh_terms: 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
chemical_list: 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