Plasmapheresis Reduces Mycophenolic Acid Concentration: A Study of Full AUC_0-12 in Kidney Transplant Recipients

Background: Mycophenolic acid (MPA), a crucial immunosuppressive drug, and plasmapheresis, an effective immunoreduction method, are simultaneously used for the management of various immune-related diseases, including kidney transplantation. While plasmapheresis has been proven efficient in removing many substances from the blood, its effect on MPA plasma levels remains unestablished.

Objectives: To evaluate the full pharmacokinetics of MPA by measuring the area under the time-concentration curve (AUC_0-12), which is the best indicator for MPA treatment monitoring after each plasmapheresis session, and to compare the AUC_0-12 measurements on the day with and on the day without plasmapheresis.

Methods: A cross-sectional study was conducted in kidney transplantation recipients who were taking a twice-daily oral dose of mycophenolate mofetil (MMF, Cellcept^®) and undergoing plasmapheresis at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, during January 2018 and January 2019. The MPA levels were measured by an enzymatic method (Roche diagnostic^®) 0, 1/2, 1, 2, 3, 4, 6, 8, and 12 h after MMF administration, for AUC_0-12 calculation on the day with and on the day without plasmapheresis sessions. Plasmapheresis was started within 4 h after administering the oral morning dose of MMF. Our primary outcome was the difference of AUC_0-12 between the day with and the day without plasmapheresis.

Results: Forty complete AUC measurements included 20 measurements on the plasmapheresis day and other 20 measurements on the day without plasmapheresis in six kidney transplant patients. The mean age of the patients was 56.2 ± 20.7 years. All patients had received 1000 mg/day of MMF for at least 72 h before undergoing 3.5 ± 1.2 plasmapheresis sessions. The mean AUC on the day with plasmapheresis was lower than that on the day without plasmapheresis (28.22 ± 8.21 vs. 36.79 ± 10.29 mg × h/L, p = 0.001), and the percentage of AUC reduction was 19.49 ± 24.83%. This was mainly the result of a decrease in AUC_0-4 of MPA (23.96 ± 28.12% reduction).

Conclusions: Plasmapheresis significantly reduces the level of full AUC_0-12 of MPA. The present study is the first to measure the full AUC_0-12 in MPA-treated patients undergoing plasmapheresis. Our study suggests that a supplementary dose of MPA is necessary for patients undergoing plasmapheresis.