Authors
Elisabet Størset, Nick Holford, Stefanie Hennig, Troels K Bergmann, Stein Bergan, Sara Bremer, Anders Åsberg, Karsten Midtvedt, Christine E Staatz
Publication date
2014/9
Journal
British journal of clinical pharmacology
Volume
78
Issue
3
Pages
509-523
Description
Aims
The aim was to develop a theory‐based population pharmacokinetic model of tacrolimus in adult kidney transplant recipients and to externally evaluate this model and two previous empirical models.
Methods
Data were obtained from 242 patients with 3100 tacrolimus whole blood concentrations. External evaluation was performed by examining model predictive performance using Bayesian forecasting.
Results
Pharmacokinetic disposition parameters were estimated based on tacrolimus plasma concentrations, predicted from whole blood concentrations, haematocrit and literature values for tacrolimus binding to red blood cells. Disposition parameters were allometrically scaled to fat free mass. Tacrolimus whole blood clearance/bioavailability standardized to haematocrit of 45% and fat free mass of 60 kg was estimated to be 16.1 l h−1 [95% CI 12.6, 18.0 l h−1]. Tacrolimus clearance was 30% higher …
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