title: Single-dose pharmacokinetics and tolerability of everolimus in stable pediatric renal transplant patients.
abstract: Everolimus (Certican; RAD), a novel macrolide with potent immunosuppressive and anti-proliferative activities, prevents acute rejection in adult recipients of renal transplantation. This phase I trial conducted in stable pediatric renal transplant patients examined the single-dose pharmacokinetics, safety, and tolerability of everolimus in combination with cyclosporin A (CsA; Neoral) and corticosteroids, with or without azathioprine. Nineteen pediatric patients were enrolled and received a single 1.2 mg/m2 dose of everolimus. Everolimus was safe and well tolerated, with a low incidence of adverse events reported and none judged to be related to the study medication. Everolimus administration did not increase infection rates or produce clinically significant changes in vital signs or changes in electrocardiograms. Apparent clearance and volume of distribution of everolimus increased with age, weight, and body surface area in a generally linear manner across the pediatric demographic ranges. Compared with adults from a previous study, apparent clearance (L/h) and distribution volume (L) were lower in pediatric patients, whereas the elimination half-life was similar. Single-dose everolimus co-administration did not affect the steady-state pharmacokinetics of CsA. Based on this information, pediatric patients will need a dose scaled down for body size, but can probably maintain the same twice-daily dosing schedule used in adults.
authors: Dialyze en Transplantatie, University Hospital Gasthuisberg, Leuven, Belgium. Rita.Lombaerts@uz.kuleuven.ac.be
authors: R
authors: R
authors: Van Damme-Lombaerts
authors: N A Y
authors: NA
authors: Webb
authors: P F
authors: PF
authors: Hoyer
authors: J
authors: J
authors: Mahan
authors: J
authors: J
authors: Lemire
authors: R
authors: R
authors: Ettenger
authors: L
authors: L
authors: McMahon
authors: N
authors: N
authors: Cambon
authors: R
authors: R
authors: Boger
authors: J M
authors: JM
authors: Kovarik
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D020123:Sirolimus / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D014181:Transplantation Immunology / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus