Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation.

Mycophenolate mofetil (MMF) is given to children in fixed doses based either on body weight or body surface area. There are data indicating mycophenolic acid (MPA) blood levels should be monitored in the early period of transplantation. However, there is little information regarding MPA pharmacokinetics (PK) in stable pediatric recipients. We evaluated MPA-PK in 20 stable renal transplant children (11.7+/-1.9 years) under long-term (46+/-31 months) MMF (26.1+/-7 mg/kg per day or 785+/-183 mg/m(2) per day) therapy plus prednisone and cyclosporin A (n=16), tacrolimus (n=3), or MMF/prednisone (n=1). Total MPA levels were measured using the EMIT-MPA assay at 0, 1, 2, 3, 4, 6, and 8 h after an oral dose of MMF. The level at 12 h was considered equal to the trough level for AUC(0-12) calculation. Mean C(0), C(max), AUC (0-12), and T(max )were 3.46+/-1.32, 13.5+/-0.58 microg/ml, 63.2+/-24.4 microg x h/ml, and 1.3+/-0.6 h, respectively. Six (30%) children were considered to have an adequate exposure (36-54 microg x h/ml) to MPA, 11 (55%) showed an AUC(0-12 )>54 microg.h/ml, and 3 (15%) showed an AUC(0-12 )<36 microg x h/ml. A C(max )>/=10 microg/ml was seen in 13 (65%) children. MMF dose did not correlate with AUC(0-12) or C(max). The combination of variables C(0), C(1), and C(4 )provided an equation to predict exposure (r(2)=0.75) where AUC(0-12)=12.62+(7.78 x C(0))+(0.90 x C(1))+(1.30 x C(2)) (P<0.001). The use of MMF without monitoring MPA blood levels may cause unnecessary overexposure to the drug in stable pediatric recipients.