title: Diagnostic efficiency of truncated area under the curve from 0 to 2 h (AUC₀₋₂) of mycophenolic acid in kidney transplant recipients receiving mycophenolate mofetil and concomitant tacrolimus.
abstract: BACKGROUND
  Recently, the use of the truncated area under the curve from 0 to 2 h (AUC(0-2)) of mycophenolic acid (MPA) has been proposed for therapeutic monitoring in liver transplant recipients. The aim of our study was the evaluation of the clinical usefulness of truncated AUC(0-2) in kidney transplant patients.
  
  
  METHODS
  Plasma MPA was measured in samples taken before the morning dose of mycophenolate mofetil, and one-half and 2 h post-dose, completing 63 MPA concentration-time profiles from 40 adult kidney transplant recipients. The AUC from 0 to 12 h (AUC(0-12)) was calculated using the validated algorithm of Pawinski et al. The truncated AUC(0-2) was calculated using the linear trapezoidal rule, and extrapolated to 0-12 h (trapezoidal extrapolated AUC(0-12)) as previously described.
  
  
  RESULTS
  Algorithm calculated and trapezoidal extrapolated AUC(0-12) values showed high correlation (r=0.995) and acceptable dispersion (ma68=0.71 μg·h/mL), median prediction error (6.6%) and median absolute prediction error (12.6%). The truncated AUC(0-2) had acceptable diagnostic efficiency (87%) in the classification of subtherapeutic, therapeutic or supratherapeutic values with respect to AUC(0-12). However, due to the high inter-individual variation of the drug absorption-rate, the dispersion between both pharmacokinetic variables (ma68=6.9 μg·h/mL) was unacceptable.
  
  
  CONCLUSIONS
  The substantial dispersion between truncated AUC(0-2) and AUC(0-12) values may be a serious objection for the routine use of MPA AUC(0-2) in clinical practice.
authors.affiliation: Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lampón
authors.forename: María J
authors.initials: MJ
authors.lastname: Tutor-Crespo
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero
authors.forename: José C
authors.initials: JC
authors.lastname: Tutor
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D009173:Mycophenolic Acid; D016559:Tacrolimus