English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

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 (95%  CI  13, 46%) and bioavailability 18% lower (95%  CI  2, 29%) in  CYP3A 5 expressers compared with non‐expressers. An  E  max  model described decreasing tacrolimus bioavailability with increasing prednisolone dose. The theory‐based model was superior to the empirical models during external evaluation displaying a median prediction error of −1.2% (95%  CI  −3.0, 0.1%). Based on simulation, Bayesian forecasting led to 65% (95%  CI  62, 68%) of patients achieving a tacrolimus average steady‐state concentration within a suggested acceptable range.    Conclusion  A theory‐based population pharmacokinetic model was superior to two empirical models for prediction of tacrolimus concentrations and seemed suitable for  B ayesian prediction of tacrolimus doses early after kidney transplantation.

Improved prediction of tacrolimus concentrations early after kidney transplantation using theory‐based pharmacokinetic modelling