Table 1.

Correlation between MMF pharmacokinetics and clinical outcomes in renal transplantationa

StudyNo. of PatientsFollow-Up TimeCalcineurin InhibitorsTDMMPA ParametersAssay MethodClinical Outcomes
Borrows et al. (55)1211 yrTacrolimusFixed dosageC0EMIT>1.60 mg/L is associated with low rejection rates; >2.75 mg/L is associated with hematologic toxicity and diarrhea
Cattaneo et al. (48)469 moCsAFixed dosageAUC0-12 h, C0HPLCAUC >40 mg·h/L or C0 >1.5 mg/L is associated with better renal functions; there was a negative correlation between free MPA levels with hematocrit levels
Hale et al. (36)1566 moCsADosage adjustment by Bayesian estimationAUC0-12 hHPLCAUC of 15 and 25 mg·h/L showed 50 and 75% maximal achievable efficacy, respectively
Kiberd et al. (50)943 moCsAFixed dosageAUC0-12 h, C0HPLCAUC of 22 mg·h/L was a threshold for prediction of acute rejection episodes
Kuypers et al. (20)221 yrTacrolimusFixed dosageC0HPLCC0 of MPA (total or free) and its metabolites did not correlate with clinical efficacy or toxicity
Mourad et al. (46)51bTacrolimusFixed dosageAUC0-12 h, C0EMITAUC of 38 mg·h/L was a threshold for toxicity (sensitivity 83%; specificity 60%)
Oellerich et al. (35)b6 moCsAFixed dosageAUC0-12 h, C0HPLCAUC of approximately 30 to 60 mg·h/L seems to be a reasonable target for early posttransplantation period
Pawinski et al. (33)333 moCsA or tacrolimusFixed dosageAUC0-12 h, C0HPLCAUC of 27.5 mg·h/L and C0 of 1.1 mg/L were threshold values for prediction of acute rejection episodes
Pillans et al. (39)271 moCsAFixed dosageAUC0-12 h, C0HPLCAUC <30 mg·h/L was associated with increased incidence of rejection; no association was found between the incidence of acute rejection and C0
van Gelder et al. (44)1546 moCsADosage adjustment by Bayesian estimationAUC0-12 h, C0bIncidence of acute rejection in low, intermediate, and high MPA concentration groups (16, 32, and 60 mg·h/L, respectively) were 28, 15, and 12%, respectively
Weber et al. (34)546 moCsAFixed dosageAUC0-12 h, C0HPLCAUC of 33.8 mg·h/L differentiates acute rejection (sensitivity 75%; specificity 64%)
  • a AUC, area under the curve; C0, predose concentration; CsA, cyclosporine; EMIT, enzyme-multiplied immunoassay technique; MMF, mycophenolate mofetil; MPA, mycophenolic acids; TDM, therapeutic drug monitoring.

  • b Not reported.