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

作者：van Boekel G A J^*; Donders A R T; Hoogtanders K E J; Havenith T R A; Hilbrands L B; Aarnoutse R E

来源：European Journal of Clinical Pharmacology, 2015, 71(7): 811-816.

DOI：10.1007/s00228-015-1863-6

• Exposure
• Limited sampling strategy
• Prolonged-release tacrolimus
• Renal transplantation

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 (AUC(0-24)) of prolonged-release tacrolimus.
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.
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): AUC(0-24) = 44.9 + 8.9 x C-0h + 2.1 x C-2h + 7.6 x 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 AUC(0-24) was worse (r (2) = 0.77) while MPPE and MAPE were 6.2 and 7.2 %, respectively.
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(.).

• 出版日期2015-7