en
Doctoral thesis
English

Application and evaluation of population pharmacokinetics for Imatinib Dosage Individualization

ContributorsGotta, Verena
Defense date2013-05-08
Abstract

Imatinib treatment for chronic myeloid leukemia (CML) could be optimized by Therapeutic Drug Monitoring (TDM). The objective of this thesis was to enhance the clinical interpretation of imatinib concentrations measured in the scope of TDM, to improve the evidence of concentration-response relationships, and to evaluate the usefulness of systematic TDM-guided dosage individualization. For this purpose, the population pharmacokinetic (PPK) approach was used and evaluated in several studies. A reference range of imatinib concentrations over the dosage interval was established through a simulation-based meta-analysis of several PPK models. From a validated in-house PPK model, a Bayesian approach for the prediction of the individual trough concentration (Cmin) was developed and validated. Correlations between individual Cmin and treatment response were confirmed in a large European patient cohort study. The clinical usefulness of systematic TDM was evaluated through a prospective randomized controlled trial. The Bayesian approach allowed easing the sampling logistics in the trial.

eng
Keywords
  • pharmakokinetics
  • pharmacodynamics
  • clinical pharmacology
  • modeling
  • tyrosine kinase inhibitor
  • monitoring
Citation (ISO format)
GOTTA, Verena. Application and evaluation of population pharmacokinetics for Imatinib Dosage Individualization. 2013. doi: 10.13097/archive-ouverte/unige:29042
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Thesis
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Technical informations

Creation07/22/2013 5:09:00 PM
First validation07/22/2013 5:09:00 PM
Update time03/14/2023 8:21:24 PM
Status update03/14/2023 8:21:24 PM
Last indexation01/29/2024 7:53:44 PM
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