Is a standard fixed dose of mycophenolate mofetil ideal for all patients?

BACKGROUND A standard fixed dose of 2 g/day of mycophenolate mofetil (MMF), irrespective of total body weight (TBW), is recommended when used in combination with cyclosporine and corticosteroids in renal transplantation. METHODS To determine the optimal MMF dose in a population with wide variation in TBW, steady-state pharmacokinetics of mycophenolic acid (MPA) was performed in 53 Asian (Chinese, Malay, Indian, Eurasian) renal transplant recipients (RTX) receiving MMF [250-1000 mg twice daily (BD)] for at least 3 months. Blood samples were collected at 0, 0.5, 1, 1.5, 2 and 6 h after the MMF dose and total MPA quantified using HPLC. RESULTS Drug exposure, as evaluated by AUC(ss, 0-12), demonstrated a significant positive correlation with TBW-adjusted MMF dose (outliers omitted: r(2) = 0.49, P < 0.0005). An AUC(ss, 0-12) of 45 mg h/l could be attained with an MMF dose of 12 mg/kg BD. CONCLUSION This study proposes that MMF should be dosed based on TBW rather than a fixed dose regimen in RTX.