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 AUC0-24 using the time points 0, 2, and 4 h after ingestion (C0h-C2h-C4h) provided the highest correlation with the AUC0-24 (r 2∈=∈0.95): AUC0-24∈=∈44.9∈+∈8.9∈×∈C0h∈+∈2.1∈×∈C2h∈+∈7.6∈×∈C4h. 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 C24h 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 C0h-C2h-C4h can be used for reliable estimation of the AUC0-24 of prolonged-release tacrolimus.