title: Comparison of cyclosporine absorption profiles over a 12-month period in stable pediatric renal transplant recipients.
abstract: Evidence suggests that the pharmacokinetic (PK) profile of microemulsion- cyclosporine A (m-CsA) during the 4-hour absorption phase represents an accurate tool to estimate drug exposure. In addition, several reports suggest a close correlation between selected single CsA concentrations at 1, 2, or 3 hours post-dose (C(1), C(2), and C(3)) and the abbreviated area under the curve (AUC)(0-4) among pediatric renal transplant patients. However, it is still unclear whether these PK correlations remain stable and reliable over 12 months posttransplant. In this study, we obtained 4-hour pharmacokinetic profiles (AUC(0-4)) from stable pediatric renal transplant recipients (phase 1) with repeat measurements 12 months later (phase 2). In addition, we evaluated the optimal single sampling point that correlated with the AUC(0-4) during both phases of the study. Over 1 year there was no significant change in the AUC(0-4) of m-CsA in pediatric renal transplant recipients. The mean dose-normalized AUC(0-4) values changed by less than 2.5%, namely, 557 versus 545 ng x h/mL per unit dose, respectively. The C(1) value was the sampling point that showed the best correlation with AUC(0-4); C(0) displayed the weakest correlation. No changes in cyclosporine dosing or glomerular filtration rate estimates were observed throughout the study period. This study demonstrates the stability of drug measurements during m-CsA therapy.
authors.affiliation: Department for Paediatric Nephrology and Dialysis of the Children's Hospital, University of Rostock, Germany. marianne.wigger@med.uni-rostock.de
authors.forename: M
authors.initials: M
authors.lastname: Wigger
authors.forename: E
authors.initials: E
authors.lastname: Drückler
authors.forename: J
authors.initials: J
authors.lastname: Muscheites
authors.forename: H J
authors.initials: HJ
authors.lastname: Stolpe
authors.forename: G
authors.initials: G
authors.lastname: Kundt
authors.forename: R
authors.initials: R
authors.lastname: Wacke
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007408:Intestinal Absorption; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine