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.
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.