title: Two-hour postdose concentration: a reliable marker for cyclosporine exposure in adolescents with stable renal transplants.
abstract: In pediatric renal transplant recipients, most patients receive maintenance treatment with cyclosporine (CsA) and mycophenolate mofetil (MMF). Until now, the 2-hour postdose CsA target level for combined maintenance treatment with MMF has not been defined. This prospective pilot study evaluated the pharmacokinetics of CsA under the influence of MMF to determine a reliable single CsA concentration time that correlates with the area under the curve (AUC(0-6h)) estimates for adolescents who were additionally treated with MMF during the late posttransplant period. The study included 13 adolescents (mean posttransplantation time, 3.5 +/- 2.55 years) with stable renal transplant function (S-Crea 121 +/- 40 micromol/L). CsA pharmacokinetic absorption profiles over a 6-hour dose interval (n = 26) were evaluated for the optimal single peak concentration using the CsA concentrations predose (C0) and at 1, 2, 3, 4, and 6 hours postdose (C1-6). Whereas C2 (mean 743.2 +/- 221.8 ng/mL) was the single point with the closest correlation to AUC(0-6h) (r2 = 0.86; P < .001), C0 (mean 120.5 +/- 35.2 ng/mL) showed the weakest correlation (r2 = 0.61, P = .002). C2 appears to be an accurate predictor of CsA exposure in adolescent kidney transplant recipients under maintenance immunosuppression in combination with MMF. Average values achieved with current dosing practices cluster around the target C2 ranges recommended for adults. The data provide a foundation for initiation of prospective clinical trials to assess the long-term risk for chronic allograft dysfunction among pediatric stable renal transplant patients in combination protocols.
authors.affiliation: Department of Pediatric Nephrology, University of Jena, Jena, Germany. ulrike.john@med.uni-jena.de
authors.forename: U
authors.initials: U
authors.lastname: John
authors.forename: S
authors.initials: S
authors.lastname: Ullrich
authors.forename: M
authors.initials: M
authors.lastname: Roskos
authors.forename: J
authors.initials: J
authors.lastname: Misselwitz
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008657:Metabolic Clearance Rate; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine