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

Abstract

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.

Key words::

• Area under the curve
• dosing frequency increase
• drug exposure
• gastrointestinal side-effects
• mycophenolic acid

Acknowledgements

We would like to thank to Dr S. Tomé from the Gastroenterology Unit for his collaboration.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.