title: C2 (2-h) levels are not superior to trough levels as estimates of the area under the curve in tacrolimus-treated renal-transplant patients.
abstract: BACKGROUND
  Recently, 2-h samples (C2) have been found superior to trough levels for therapeutic monitoring of transplanted patients receiving cyclosporin. The present study was undertaken to see if the same was the case for tacrolimus.
  
  
  METHODS
  Blood tacrolimus levels were determined in 21 consecutive patients at 3 and 14 days after renal transplantation, and before and 1, 2, 3, 4, and 6 h after oral intake of 0.1 mg/kg tacrolimus. The area under the blood concentration/time curve (AUC) was determined by the trapezoidal method, association between blood concentration at each sampling time and AUC by Pearson's correlation coefficient, and pairs of correlation coefficients were compared by an asymptotic Wald-type test.
  
  
  RESULTS
  AUC varied five-fold despite near-equal dosing. Pearson's correlation coefficient for trough level, 1, 2, 3, 4, and 6 h were 0.84, 0.60, 0.81, 0.95, 0.95, and 0.94 on day 3 and 0.94, 0.69, 0.92, 0.96, 0.94, 0.92 on day 14. Three-, 4- and 6-h levels had significantly higher correlation coefficients compared to trough, 1- and 2-h levels. One-hour samples had significantly lower correlation coefficients compared to all other sampling times on day 14. The patient with the highest AUC developed nephrotoxicity despite trough levels in the desired range.
  
  
  CONCLUSIONS
  Two-hour levels are not superior to trough levels in tacrolimus-treated renal transplant patients. Despite good correlation between trough level and AUC, some patients may still receive nephrotoxic doses despite trough levels in the desired range. Sampling 3-6 h after oral intake may be at least as good as trough levels.
authors.affiliation: Department of Renal Medicine C, Skjeby Sygehus, Arhus University Hospital, Denmark. kaj@dadlnet.dk
authors.forename: Kaj
authors.initials: K
authors.lastname: Jørgensen
authors.forename: Johan
authors.initials: J
authors.lastname: Povlsen
authors.forename: Søren
authors.initials: S
authors.lastname: Madsen
authors.forename: Melvin
authors.initials: M
authors.lastname: Madsen
authors.forename: Hans
authors.initials: H
authors.lastname: Hansen
authors.forename: Asger
authors.initials: A
authors.lastname: Pedersen
authors.forename: Else-Marie
authors.initials: EM
authors.lastname: Heinsvig
authors.forename: Jørgen
authors.initials: J
authors.lastname: Poulsen
mesh_terms: D019540:Area Under Curve; D005215:Fasting; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D011184:Postoperative Period; D011446:Prospective Studies; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus