Many drugs exhibit major variability in both pharmacokinetic (PK) and pharmacodynamic (PD) parameters that prevents the use of the same dose for all patients. Variability can occur both between patients (IIV) as well as within patients over the course of time (IOV). In a drug with narrow therapeutic range and substantial IIV, dose selection may require individual adaptation. Adaptation can either be made before (a priori) or after (a posteriori) first drug administration. The former implies basing the dose on prior information known to be influential, such as kidney function indicators, weight or concomitant medication, whereas a posteriori dose adaptations are based on post-treatment observations. Often individualization cannot be based on the clinical outcome itself. In such cases, drug concentrations or biomarkers may be valuable for dose individualisation …
Contents
Introduction
Dose selection
The dose-response relationship
A priori dosing
A posteriori dosing
Population modelling
Basic principles
Modelling TDM data
The therapeutic areas
Immunosuppression in paediatric transplantation
Myelosuppression in anticancer treatment
Aim of the thesi
Methods used
Description of data
Tacrolimus in paediatric transplantation
Myelosuppression
Modelling and simulation
Population analysis
Simulation studies
Dosing tool
Results
Models for tacrolimus PK in paediatric transplantation
Patients and data collection
Bayesian forecasting with previously developed models
Population modelling
Dose revision
Variability parameters in the myelosuppression model
System related covariates
Interoccasion variability
Dose optimisation with nadir level as target
Bayesian dose adaptation in Excel
Dosing tool for intravenous tacrolimus
Dosing tool for neutrophil nadir as target
Author: Wallin, Johan
Source: Uppsala University Library
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