title: Graft outcome and mycophenolic acid trough level monitoring in kidney transplantation.
abstract: BACKGROUND
  Large inter- and intrapatient variabilities have been observed in the pharmacokinetics of mycophenolic acid (MPA). As a consequence, the efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic drug monitoring.
  
  
  METHODS
  In this retrospective study we analyzed; 7536 12-hour trough MPA samples obtained during the first year posttransplantation among 314 kidney recipients treated with tacrolimus, MMF, and corticosteroids.
  
  
  RESULTS
  Despite taking similar MMF doses, patients with delayed graft function (DGF) showed lower 12-hour trough MPA levels than patients without DGF 1.4 +/- 0.1 vs 2.1 +/- 0.1 microg/mL; P = .001). There was a significant correlation between 12-hour trough MPA levels and creatinine clearance (r = .32; P < .001). Logistic regression analysis showed that creatinine clearance was a predictive factor of adequate 12-hour trough MPA levels (>1.6 microg/mL) at 7 days posttransplantation. Twelve-hour trough MPA levels at 7 days posttransplantation were lower among patients who developed an acute rejecton episode (1.5 +/- 0.1 vs 2.1 +/- 0.1 microg/mL; P < .001), whereas those with gastrointestinal side effects showed high levels (4.1 +/- 0.5 microg/mL).
  
  
  CONCLUSIONS
  In patients with delayed or poor graft function, MMF doses greater than 2 g/d may be necessary to achieve adequate MPA levels. Therapeutic drug monitoring of MPA may be useful to prevent acute rejection episodes or toxicity.
authors.affiliation: Department of Nephrology, Hospital Clínico San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
authors.forename: A I
authors.initials: AI
authors.lastname: Sánchez Fructuoso
authors.forename: M A Moreno
authors.initials: MA
authors.lastname: de la Higuera
authors.forename: P
authors.initials: P
authors.lastname: Garcia-Ledesma
authors.forename: M
authors.initials: M
authors.lastname: Giorgi
authors.forename: F
authors.initials: F
authors.lastname: Ramos
authors.forename: N
authors.initials: N
authors.lastname: Calvo
authors.forename: I
authors.initials: I
authors.lastname: Pérez-Flores
authors.forename: A
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid