title: Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients.
abstract: MPA is an immunosuppressive agent used to prevent graft rejection after renal transplantation. MPA shows considerable inter- and intraindividual variability in exposure in children and has a defined therapeutic window, and TDM is applied to individualize therapy. We aimed to study the exposure to MPA measured as the AUC in pediatric renal transplant patients, to identify factors influencing exposure and to assess target attainment. Children transplanted between 1998 and 2014 in a single center were included. Two groups were identified: Group 1 (AUC <3 wk post-transplantation) and Group 2 (AUC >18 months post-transplantation). Therapeutic targets were set at: AUC0-12h of 30-60 mg h/L. A total of 39 children were included in Group 1 (median age 13.3 yr) vs. 14 in Group 2 (median age 13.4 yr). AUC0-12h was 29.7 mg h/L in Group 1 and 56.6 mg h/L in Group 2, despite a lower dosage in Group 2 (584 and 426 mg/m(2) , respectively). About 46% of patients reached the target AUC0-12h in Group 1. Time since transplantation and serum creatinine were significantly associated with MPA exposure (p < 0.001), explaining 36% of the variability. Individualization of the mycophenolate dose by more intense and more early TDM could improve target attainment.
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Health Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Martial
authors.affiliation: Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Bart A W
authors.initials: BA
authors.lastname: Jacobs
authors.affiliation: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Cornelissen
authors.affiliation: Radboud Institute for Health Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: Anton F J
authors.initials: AF
authors.lastname: de Haan
authors.affiliation: Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Birgit C P
authors.initials: BC
authors.lastname: Koch
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Health Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Health Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.affiliation: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michiel F
authors.initials: MF
authors.lastname: Schreuder
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Health Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: Roger J M
authors.initials: RJ
authors.lastname: Brüggemann
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: children; immunosuppressive agents; pharmacokinetics; therapeutic drug monitoring; transplantation