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Novel pharmacometric techniques to quantify the pharmacodynamics of analgesics

The overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics.

Goulooze, S.C.
03 November 2020
Thesis in Leiden Repository

The overarching clinical aim of this thesis was to improve pharmacological pain management by characterising the pharmacodynamics of analgesics. To achieve this aim, available advanced pharmacometric modelling approaches are used to maximise the information that can be obtained from the available clinical data.

New tools and approaches
To address methodological gaps for pharmacodynamic analysis, we introduced two new model development tools, as well as two new pharmacodynamics modelling approaches for the characterisation of iatrogenic withdrawal syndrome in children. In addition to expanding our pharmacodynamic knowledge, this work can increase the clinical applicability of existing pharmacokinetic models: knowing what drug concentrations will give desirable clinical outcomes, we can use pharmacokinetic models to evaluate if an analgesic dose regimen is likely to produce this concentration.

Bas Goulooze

Starting point for further research
The models developed in this thesis can serve as a starting point for further research into the pharmacodynamics of analgesics by extending these models to include additional patient populations or other analgesics. Moreover, the novel pharmacometric techniques that were introduced in this thesis can support future analyses in a variety of settings: repeated time-to-event data, iatrogenic withdrawal syndrome data, and composite clinical scale data.

Goulooze: ‘With the new tools that we developed, we advanced the field of pharmacodynamics research and helped address long-standing clinical questions on the optimal treatment of pain.’

With this dissertation, Goulooze gave a new impulse to research into the pharmacodynamics of pain and withdrawal, a subject on which little progress had been made. His scientific work was awarded the prestigious Lewis Sheiner Student Session Prize towards the end of his PhD trajectory in 2019, and he obtained his PhD cum laude.

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