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 μg.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)) ≤ 40 μg.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.