Dataset Information

Limited sampling strategy for prolonged-release tacrolimus in renal transplant patients by use of the dried blood spot technique.

ABSTRACT:

Purpose

The aim of this study was to develop a clinically applicable limited sampling strategy for ambulatory Caucasian kidney transplant patients to estimate area under the curve in a 24-h period (AUC0-24) of prolonged-release tacrolimus.

Methods

Twenty six kidney recipients, at least 6 months after transplantation, receiving prolonged-release tacrolimus, were enrolled. In each patient, seven blood samples were collected during a period of 24 h by use of the validated dried blood spot method. Best subset selection multiple linear regression was performed to derive limited sampling strategy (LSS). The equations were constrained to include a maximum of three samples collected within 4 h after the intake to maintain clinical applicability. To assess the predictive performance of LSS, residuals for each patient were calculated based on models fitted to a dataset where that patient was omitted.

Results

The prediction formula for the AUC(0-24) using the time points 0, 2, and 4 h after ingestion (C(0h)-C(2h)-C(4h)) provided the highest correlation with the AUC(0-24) (r(2)?= 0.95): AUC0-24 = 44.9 + 8.9 × C(0h)?+ 2.1 × C(2h)?+ 7.6 × C(4h). Measures for bias and precision, i.e., median percentage prediction error (MPPE) and median absolute prediction error (MAPE), were 0.4 and 4.8%, respectively. For the same patients, the correlation between C(24h) and AUC0-24 was worse (r(2)?= 0.77) while MPPE and MAPE were 6.2 and 7.2%, respectively.

Conclusion

In the outpatient department, a LSS using C(0h)-C(2h)-C(4h) can be used for reliable estimation of the AUC(0-24) of prolonged-release tacrolimus.

SUBMITTER: van Boekel GA

PROVIDER: S-EPMC4464598 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Limited sampling strategy for prolonged-release tacrolimus in renal transplant patients by use of the dried blood spot technique.

van Boekel G A J GA Donders A R T AR Hoogtanders K E J KE Havenith T R A TR Hilbrands L B LB Aarnoutse R E RE

European journal of clinical pharmacology 20150517 7

<h4>Purpose</h4>The aim of this study was to develop a clinically applicable limited sampling strategy for ambulatory Caucasian kidney transplant patients to estimate area under the curve in a 24-h period (AUC0-24) of prolonged-release tacrolimus.<h4>Methods</h4>Twenty six kidney recipients, at least 6 months after transplantation, receiving prolonged-release tacrolimus, were enrolled. In each patient, seven blood samples were collected during a period of 24 h by use of the validated dried blood ...[more]

PMID: 25980838

Similar Datasets

Project description:BackgroundThe optimal dose of mycophenolate mofetil (MMF) in renal transplant patients has been recommended to be decided on the basis of area under the concentration-time curve (AUC0-12) of mycophenolic acid (MPA). Although meta-analysis has revealed that postoperative day (POD) is an influencing factor in MPA pharmacokinetics, there are no reports regarding a limited sampling strategy (LSS) for MPA AUC in consideration of POD. The aim of this study was to construct of an LSS considering POD that appropriately expresses the MPA AUC following renal transplantation and evaluation of the usefulness.MethodsSerum concentration-time profiles (measured AUC0-12) comprising nine sampling points over 12 h were analyzed in 36 living-donor renal transplant recipients after MMF administration with concomitant once-daily prolonged-release tacrolimus. Two LSSs were developed by stepwise multiple regression analysis (Method A: not classified by PODs; Method B: classified by PODs into POD?<?31 and POD???31). Each LSS comprised four blood-sampling points within 6 h after MMF administration. Precision and reliability were verified by using root-mean-square error (RMSE), correlation coefficient (R2), and coefficient of determination (q2) by using leave-one-out cross-validation. The absolute values of the difference between measured and estimated AUCs (delta AUC) were compared for both estimating equations.ResultsOne-hundred samples obtained from 36 recipients for AUC0-12 comprised POD?<?31 (n?=?39) and POD???31 (n?=?61). Estimation of AUC0-12 by Method B resulted in better accuracy and reliability (Method A: RMSE?=?5.5, R2?=?0.85, q2?=?0.83; Method B: POD?<?31: RMSE?=?5.5, R2?=?0.86, q2?=?0.83; POD???31: RMSE?=?3.9, R2?=?0.92, q2?=?0.89) and significantly lower median delta AUC compared with that by Method A (delta AUC: 2.6 (0.0-11.6) v.s. 3.9 (0.1-18.1), p?=?0.032).ConclusionThese results suggest that LSS, classified as POD?<?31 or POD?>?31, would provide more accurate and reliable estimation of MPA AUC0-12 in Japanese living-donor renal transplant patients.

Project description:BACKGROUND:An extended-release, once-daily, oral formulation of tacrolimus is currently used after kidney transplantation as a substitute for the conventional twice-daily formulation. The purpose of this study was to provide a limited sampling strategy with minimum and optimum sampling points to predict the tacrolimus area under the concentration-time curve (AUC) after administration of once-daily tacrolimus in de novo adult kidney transplant patients. METHODS:A total of 36 adult Japanese kidney transplant patients receiving once-daily tacrolimus were included: 31 were allocated to a study group to develop limited sampling strategy (LSS) model equations based on multiple stepwise linear regression analysis, and 5 were allocated to a validation group to estimate the precision of the LSS equations developed by the study group. Twelve-hour AUC (AUC0-12) was calculated by the trapezoidal rule, and the relationship between individual concentration points and AUC0-12 were determined by multiple linear regression analysis. The coefficient of determination (R2) was used to assess the goodness-of-fit of the regression models. Three error indices (mean error, mean absolute error, and root mean squared prediction error) were calculated to evaluate predictive bias, accuracy, and precision, respectively. Quality of the statistical models was compared with Akaike's information criterion (AIC). RESULTS:A four-point model using C0, C2, C4 and C6 gave the best fit to predict AUC0-12 (R2 = 0.978). In the three- and two-point models, the best fits were at time points C2, C4, and C6 (R2 = 0.973), and C2 and C6 (R2 = 0.962), respectively. All three models reliably estimated tacrolimus AUC0-12, consistent with evaluations by the three error indices and Akaike's information criterion. Practically, the two-point model with C2 and C6 was considered to be the best combination, providing a highly accurate prediction and the lowest blood sampling frequency. CONCLUSIONS:The two-point model with C2 and C6 may be valuable in reducing the burden on patients, as well as medical costs, for once-daily tacrolimus monitoring.

Dataset Information

Limited sampling strategy for prolonged-release tacrolimus in renal transplant patients by use of the dried blood spot technique.

Purpose

Methods

Results

Conclusion

Publications

Limited sampling strategy for prolonged-release tacrolimus in renal transplant patients by use of the dried blood spot technique.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets