A limited sampling strategy for estimation of the area under the curve (0 to 8 hours) of mycophenolic acid administered three times daily to liver transplant recipients

Objectives. Gastrointestinal side-effects caused by mycophenolic acid (MPA) are frequent in liver transplant recipients, and in these cases a switch from two to three daily doses is usually recommended. However, a limited sampling strategy for the estimation of MPA area under the curve from 0 to 8 hours (AUC((0--8h))) has not been made. Design and methods. In 22 liver transplant patients who were administered MPA three times daily, the trapezoidal extrapolated MPA AUC((0--8h)) values using a sampling time from 0 to 2 hours were calculated. Results. A tentative therapeutic range for MPA AUC((0--8h)) of about 20--40 mu mu g.h/mL is proposed, and in the 13 patients with supratherapeutic values the total leukocyte blood count was significantly lower than in the 9 patients with AUC((0--8h)) < a parts per thousand currency sign 40 mu mu g.h/mL (P < 0.001). Significant negative correlations were found between the total leukocyte blood count and the MPA trough levels (r == --0.458; P < 0.05), AUC((0--8h)) (r == --0.479; P < 0.05), and AUC((0--2h)) (r == --0.437; P < 0.05). A significant correlation was found between the trapezoidal extrapolated AUC((0--8h)) and trapezoidal AUC((0--2h)) results (r == 0.850; P < 0.001). Conclusions. The trapezoidal extrapolated AUC((0--8h)), and possibly trapezoidal AUC((0--2h)), may be useful for routine therapeutic MPA monitoring in liver transplant recipients in which the dosing frequency is increased from twice to three times a day.