title: Reduced variability of neoral pharmacokinetic studies in pediatric renal transplantation.
abstract: In adult renal transplant recipients the Neoral area under the curve (AUC) displays less inter- and intra-individual variability than Sandimmune, and those renal transplant recipients with reduced intra-individual variability of the AUC have a lower risk for chronic rejection. As variability of Neoral pharmacokinetic (Pk) parameters has not been investigated in pediatric renal transplant recipients, we retrospectively analyzed 453 Pk profiles in 14 pediatric patients who were switched from Sandimmune to Neoral and compared the inter- and intra-individual variability of the Pk profiles on both formulations. After the switch, we observed less inter- and intra-individual variability of AUC, the 2-h concentration, and the oral clearance. As clearance with both formulations is supposedly equal, the significantly lower intra-individual variability of oral clearance is most likely an effect of less variable absorption. While the lower inter-individual variability of the Pk parameters suggests increased success in keeping cyclosporine concentrations on target, the lower intra-individual variability leads to the hypothesis that with Neoral, a lower incidence of chronic rejection might be achieved.
authors.affiliation: Division of Pediatric Nephrology and Hypertension, University of Texas-Houston, Medical School, 77030, USA. ronald.portman@uth.tmc.edu
authors.forename: H U
authors.initials: HU
authors.lastname: Meier-Kriesche
authors.forename: R
authors.initials: R
authors.lastname: Swinford
authors.forename: B D
authors.initials: BD
authors.lastname: Kahan
authors.forename: P
authors.initials: P
authors.lastname: Brannan
authors.forename: R J
authors.initials: RJ
authors.lastname: Portman
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008657:Metabolic Clearance Rate; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine