Intra-individual variability of mycophenolic acid concentration according to renal function in liver transplant recipients receiving mycophenolate monotherapy

Abstract

BACKGROUNDS/AIMS: Mycophenolate mofetil (MMF) has wide inter- and intra-individual variability of mycophenolic acid (MPA) after liver transplantation (LT). On this study, we aimed to analyse the intra-individual variability of MPA concentration in stable adult LT recipients receiving MMF monotherapy and develop a method to determine the target level in the situation of wide intra-individual variability. METHODS: This retrospective cross-sectional study included 30 LT recipients. All patients received MMF monotherapy at a dose of 500 mg twice daily for >/=2 years and were divided into two groups based on renal function. MPA concentration-associated values were presented as mean with standard deviation and coefficient of variation (CV). RESULTS: The normal renal function group (n=15) showed a mean 12-hour MPA concentration of 2.5+/-0.5 microg/ml (range, 1.8+/-0.5 to 3.6+/-0.7 microg/ml) and a mean CV of 20.4+/-7.7% (range, 8.7% to 39.4%). In the renal dysfunction group (n=15), the 12-hour MPA concentration fluctuated more widely with a mean value of 3.7+/-0.9 microg/ml (range, 2.8+/-0.8 to 5.1+/-1.2 microg/ml) and a mean CV of 24.5+/-4.9% (range, 17.1% to 37.5%). The 12-hour MPA concentration was significantly higher in the renal dysfunction group, as compared to the normal renal function group (p=0.001); whereas, the CV was not significantly different between the two groups (p=0.093). CONCLUSIONS: We determined the inter- and intra-individual variability of 12-hour MPA concentration after LT. The results suggested that therapeutic drug monitoring of MPA is necessary due to the inter-individual and intra-individual variability of MMF pharmacokinetics, especially in LT recipients with renal dysfunction.