title: Monitoring of mycophenolic acid predose concentrations in the maintenance phase more than one year after renal transplantation.
abstract: BACKGROUND
  Routine therapeutic drug monitoring of mycophenolic acid (MPA) is generally performed using the area under the concentration-time curve from 0 to 12 hours (AUC0-12) with recommended values between 30 and 60 μg·h/mL.
  
  
  OBJECTIVE
  The aim of this study was to examine whether the monitoring of the MPA predose concentration (C0) in patients who are stable for >1 year after renal transplantation was practical and to determine factors that cause MPA C0 variability among patients.
  
  
  METHODS
  Eighty-six Japanese patients who had undergone renal transplantation and were taking tacrolimus and who had their MPA C0 analyzed >6 times by high-performance liquid chromatography for >1 year posttransplantation were enrolled.
  
  
  RESULTS
  Recipients with MPA AUC0-12 levels<30 μg·h/mL on day 28 and 1 year after transplantation had an MPA C0 of <2.0 μg/mL, with a sensitivity of 90.9% and a specificity of 70.7%. There was no significant difference in the mean dose-adjusted MPA C0>1 year after transplantation between subjects with either the UGT (1A1, 1A9, and 2B7) or drug transporter (SLCO1B3, ABCC2, and ABCG2) genotypes. However, in a multiple regression analysis, the dose-adjusted mean MPA C0>1 year after transplantation was significantly associated with age (P=0.0035), creatinine clearance (P=0.0001), and the dose-adjusted MPA AUC0-12 at 1 year (P=0.0147).
  
  
  CONCLUSIONS
  To keep the MPA AUC0-12>30 μg·h/mL, the plasma threshold for maintaining the MPA C0 with tacrolimus should be set >2.0 μg/mL as determined by high-performance liquid chromatography. For patients who are stable for >1 year after transplantation, continued monitoring of the MPA C0 using the same samples used to monitor the tacrolimus C0 and the additional assessment of the MPA AUC0-12 at the 1-year time point seem to be a viable option. If a change of the mycophenolate mofetil dose seems necessary based on the routine MPA C0 information, the determination of MPA AUC0-12 using a limited sampling strategy is recommended.
authors.affiliation: Department of Pharmacy, Akita University Hospital, and Department of Urology, Akita University School of Medicine, Akita, Japan. m-miura@hos.akita-u.ac.jp
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Kato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagaya
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
mesh_terms: D000328:Adult; D000367:Age Factors; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D009173:Mycophenolic Acid / Q000097:blood* / Q000627:therapeutic use*; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors
chemical_list: C000715087:ABCC2 protein, human; D007166:Immunosuppressive Agents; D000089762:Multidrug Resistance-Associated Protein 2; D009173:Mycophenolic Acid; D016559:Tacrolimus