Mycophenolic acid exposure in high-and low-weight renal transplant patients after dosing with mycophenolate mofetil in the opticept trial

The Opticept trial was an open-label, randomized, multicenter trial involving 720 kidney recipients. Three immunosuppressant dosing regimens were evaluated, including both fixed and concentration-controlled dosing of mycophenolate mofetil in combination with standard and reduced calcineurin inhibitor levels. Mycophenolic acid (MPA) levels were measured, yielding one of the largest databases to assess the impact of variables on MPA exposure. The present subset analysis evaluated the effect of baseline body weight in three noncontiguous weight categories on MPA exposure at steady state (Day 90) in patients receiving tacrolimus. Multivariate linear regression models assessed the relationship between area under the concentration-time curve (AUC) and several variables. In all, 219 patients had baseline weights in the three categories and an MPA AUC at Day 90: 50 kg or less (n = 12, all female); 60 to 80 kg (n = 136); or 100 kg or greater (n = 71). In overall comparisons by weight class, clearance increased with increased weight, resulting in an inverse relationship between dose-corrected MPA AUCs and weight at Day 90 (P < 0.0001). In patients of extreme weight, wide disparities of MPA exposure were measured despite the mean mycophenolate mofetil dose, notably in those 50 kg or less who had comparatively high dose-corrected MPA AUCs. Patients at the extremes of weight might be at risk of over-or underimmunosuppression unless doses are adjusted.