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Monitoring of Mycophenolic Acid Predose Concentrations in the Maintenance Phase More Than One Year After Renal Transplantation

Miura, Masatomo PhD*; Niioka, Takenori PhD*; Kato, Shoutaro BS*; Kagaya, Hideaki PhD*; Saito, Mitsuru MD; Habuchi, Tomonori MD, PhD; Satoh, Shigeru MD, PhD†‡

Therapeutic Drug Monitoring: June 2011 - Volume 33 - Issue 3 - p 295-302
doi: 10.1097/FTD.0b013e3182197e38
Original Article

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.

From the *Department of Pharmacy, Akita University Hospital; †Department of Urology, Akita University School of Medicine; and ‡Division of Renal Replacement Therapeutic Science, Department of Urology Akita University School of Medicine, Akita, Japan.

Received for publication November 24, 2010; accepted March 9, 2011.

Supported by grants from the Japan Research Foundation for Clinical Pharmacology, Tokyo, Japan, and the Research Foundation for Pharmaceutical Sciences, Tokyo, Japan.

The authors declare no conflicts of interest.

Correspondence: Masatomo Miura, PhD, Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan (e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.