Modeling of Tacrolimus Exposure in Kidney Transplant According to Posttransplant Time Based on Routine Trough Concentration Data

Autor: Nadia, Ben Fredj, Jean Baptiste, Woillard, Jean, Debord, Amel, Chaabane, Naceur, Boughattas, Pierre, Marquet, Franck, Saint-Marcoux, Karim, Aouam
Rok vydání: 2016
Předmět:
Zdroj: Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 14(4)
ISSN: 2146-8427
Popis: The aim of this study was to develop a pharmacokinetics model allowing the description of the evolution of tacrolimus exposure in kidney transplant patients over the first months after transplant, using trough concentrations of routinely collected blood.The authors performed a retrospective analysis of trough concentration data collected from adult kidney transplant recipients (from 2008 to 2013). The total data set was divided into a building data set, used to build the structural model, and a validation data set, used to validate the structural model. (C0 = 133; 26 patients). A pharmacokinetics analysis was carried out by applying a nonparametric adaptive grid approach. The structural model parameters were tacrolimus clearance and volume of distribution.In patients in the building set group, estimated clearance was 3.6 ± 0.57 L/h and estimated volume of distribution was 9.9 ± 1.14 L. No covariate was significantly associated with tacrolimus clearance or volume of distribution. The model adequately described tacrolimus dose-normalized trough concentration evolution after transplant (the plot of individual model predicted versus observed concentrations resulted in r = 0.84). The prediction performance in the validation group yielded 2.3% mean prediction error and 21.4% root mean squared error.This model could be highly useful in the optimization of tacrolimus prescription at any posttransplant time in kidney transplant patients.
Databáze: OpenAIRE