title: Evaluation of a limited sampling strategy to estimate area under the curve of tacrolimus in adult renal transplant patients.
abstract: Limited sampling strategies have been developed to predict full AUCs. The goal of this study was to develop a limited sampling strategy to estimate the AUC of tacrolimus in adult renal transplant patients and to evaluate its predictive performance in an independent patient population. A total of 27 tacrolimus pharmacokinetic profiles were studied. Blood samples were collected before the dose (0) and at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. The study was divided into 2 phases. In phase 1, the goal was to obtain a sampling strategy from 14 pharmacokinetic profiles. In phase 2, the bias and precision of the model were evaluated in another 13 pharmacokinetic profiles. The best correlation was achieved at 4 hours after dose (r(2) = 0.790). Stepwise multiple regression analysis determined that the abbreviated AUC at 0, 1, and 4 hours could accurately predict total AUC (r(2) = 0.965). The following formula was developed: AUC = 8.90 + 4.0C0h+ 1.77C1h + 5.47C4h. No significant differences were found between calculated and estimated AUC (165.6 +/- 41.1 and 166.7 +/- 43.2 ng.h/mL, respectively). The mean prediction error (MPE), the relative prediction error (PE), and the mean squared error (MSE) were 0.48 ng.h/mL, 0.16%, and 40.0 ng.h/mL, respectively. The limited sampling with use of the 3 levels at 0, 1, and 4 hours postdose provides accurate, reliable determination of tacrolimus AUC in renal transplant patients.
authors.affiliation: Biochemistry Service, Vall d' Hebron Teaching Hospital, University of Barcelona, Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Armendáriz
authors.forename: Leonor
authors.initials: L
authors.lastname: Pou
authors.forename: Carme
authors.initials: C
authors.lastname: Cantarell
authors.forename: Rosa
authors.initials: R
authors.lastname: Lopez
authors.forename: Manuel
authors.initials: M
authors.lastname: Perelló
authors.forename: Lluis
authors.initials: L
authors.lastname: Capdevila
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008875:Middle Aged; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus