Mycophenolic acid (MPA) is the active component of mycophenolate mofetil (MMF). Low MPA exposure is associated with a higher incidence of acute GVHD and possibly worse engraftment. Therapeutic plasma targets have been proposed in hematopoietic cell transplantation (HCT), however, are difficult to achieve in adult patients with MMF doses of 2 g/day. Mycophenolate pharmacokinetics was prospectively studied in adults undergoing nonmyeloablative HCT who received MMF 3 g/day with CYA. The first 15 individuals received 1.5 g every 12 h and the second 15 received 1 g every 8 h. Sampling was performed in each patient with i.v. and oral administration. There were no differences in total or unbound MPA 24-h cumulative area under the curves (AUCs), concentrations at steady state (Css) or troughs between the two dosing regimens (all P>0.01). The previously proposed total MPA Css target of 3 μg/ml and trough ≥1 μ/ml were achieved in only 13-27% and 20-53% of patients, respectively, on 3 g/day. However, the 3 g/day regimens readily achieved satisfactory unbound 24-h cumulative AUC targets of 0.600 μg*h/ml in 87-100% of subjects. There appears to be no significant difference in daily MPA exposure when MMF of 3g/day is divided into two or three equal doses.
Bibliographical noteFunding Information:
This work was supported by grants from the National Institutes of Health (NIH), National Cancer Institute 5K23CA096622 (PJ) and a seed grant from the University of Minnesota Academic Health Center (PJ). The expert technical assistance of Jason Dagit and Jim Fisher is gratefully acknowledged.
Drs Jacobson and Weisdorf have in the past received financial support from Roche Pharmaceuticals.