title: Within-patient variability of mycophenolic acid exposure: therapeutic drug monitoring from a clinical point of view.
abstract: Exposure to mycophenolic acid (MPA) is highly variable among patients on standard dose mycophenolate mofetil (MMF) therapy. In addition, MPA exposure increases with time posttransplant and exposure is predictive for the development of acute rejection. Consequently, therapeutic drug monitoring (TDM) of MPA may improve clinical outcome, although a large within-patient variability could be a limitation. This study was designed to analyze the extent of within-patient variability of MPA exposure for area-under-the-curve (AUC0-12) and pre-dose concentrations (C0). For 9 occasions during the first 5 months after transplantation, AUC0-12 and C0 values from 45 renal transplant recipients, all using cyclosporine and corticosteroids, were divided into quartiles. When AUC0-12 or C0 changed 1, 2, or 3 quartiles within a patient from one occasion to the next, a score of respectively 1, 2, or 3 points was assigned. Doing this for all 8 between occasion intervals, the maximal score for within-patient variability could be 8 x 3 = 24 per patient. For AUC0-12, the median overall score was 3.4 of maximal 24. For C0 measurements, this score was significantly higher: 6.0 (P < 0.001). The higher overall score for C0 was explained by more quartile changes during the first weeks after transplantation. It is concluded that within-patient variability for MPA exposure is low in kidney transplant recipients during the first 5 months after transplantation. In the first weeks after transplantation, within-patient variability is larger for C0 than for AUC0-12.
authors.affiliation: Department of Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus University Medical Center, Rotterdam, The Netherlands. r.vanhest@erasmusmc.nl
authors.forename: Reinier M
authors.initials: RM
authors.lastname: van Hest
authors.forename: Ron A
authors.initials: RA
authors.lastname: Mathot
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Jan N
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid