Variability of mycophenolate mofetil trough levels in stable kidney transplant patients

Abstract

Great interindividual variability in the pharmacokinetics of mycophenolate mofetil (MMF) exists among kidney transplanted patients. The within-patient variability in stable transplanted patients is not well established. We performed 258 determinations of trough MMF levels in 86 stable transplant patients without hematological or gastrointestinal toxicity after at least year of a functioning kidney and a fixed dose of MMF. We examined the within-patient variability of levels related with clinical factors (age, gender, underlying cause of kidney failure, time since transplant, associated immunosuppression, and MMF dose) and analytical factors (serum creatinine, proteinuria, hemoglobin). Trough MMF levels were 3.6 mg/L, percentile (Pc) 25 1.6 mg/L, Pc 75 4.4 mg/L with intraindividual variability median of 65% (Pc 25 14%, Pc 75 79%). For the data analysis a variation of 14% was chosen, which corresponded to the 25th percentile. We did not observed differences between patients with variation below or above the Pc 25 in age, gender, underling cause of kidney failure, basal MMF levels, and MMF dose. Patients with greater variations showed significantly higher serum creatinine and proteinuria values than the others (1.84 +/- 0.54 vs 1.46 +/- 0.44 mg/dL and 0.45 +/- 0.42 vs 0.19 +/- 0.14 g/L; P < .05). Therefore, great within-patient variability in trough MMF levels was associated with poor kidney function and proteinuria.