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.
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: David K Metz; Nick Holford; Joshua Y Kausman; Amanda Walker; Noel Cranswick; Christine E Staatz; Katherine A Barraclough; Francesco Ierino Journal: Transplantation Date: 2019-10 Impact factor: 4.939