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.

Therapeutic Monitoring of Calcineurin Inhibitors for the Nephrologist

“…Two trials showed that the tacrolimus C 0 correlated poorly with AUC (r 2 ϭ 0.11 and 0.362) and that C 4 was the best single-point correlate of AUC (r 2 ϭ 0.79 and 0.81). Both studies suggested that a two-or three-point limited sampling strategy, both of which incorporated C 4 , would predict AUC better than C 0 levels (63,64). Other studies identified C 2 or C 3 as the best correlates of AUC (65,66).…”

Pharmacokinetics of tacrolimus in stable paediatric renal transplant recipients

“…Especially in the early post-transplant period, the reliance on only Tac TLs results in over-or underestimation of the current Tac exposure. Otherwise, a full PK profile requires the child to be observed for 12 h Abbreviated AUC monitoring, which overcomes the inconvenience to the patient, has already been introduced and used for adults [9,10], yet, for children, very little literature is available. Therefore, we investigated the correlation of Tac TL and 0-12 h AUC, and the use of limited sampling strategies, in paediatric renal transplant recipients whose condition was stable.…”

Pathophysiological idiosyncrasies and pharmacokinetic realities may interfere with tacrolimus dose titration in liver transplantation

“…Depending on the t 1/2 and the dosing interval, the current C min can be affected by more or less of the previous doses before steady state was reached. [22][23][24][25], but besides being better than C min , their clinical utility is scarce.…”