Pharmacokinetics, pharmacodynamics and safety of different propofol formulations.
Comparative pharmacology in rats, surgical patients, intensive care patients and children.


Dr. C.A.J. Knibbe, St. Antonius ziekenhuis Nieuwegein
Promotor: M. Danhof. Co-promotores: L.P.H.J. Aarts en P.F.M. Kuks, St. Antonius Ziekenhuis Nieuwegein
Propofol is a popular drug for intensive care sedation in adults.
However, the associated fat load may lead to complications, in particular when used for long-term sedation in special patient groups, such as critically ill patients and children.
Therefore, we have developed a new formulation of propofol with a lower fat content. We have compared this formulation with other propofol products in various populations, ranging from rats to special patient groups. For the latter populations, the application of advanced data analysis techniques, such as population pharmacokinetic-pharmacodynamic modelling, has proven to be of great value. This population approach enables the identification of predictors of variability which may facilitate individual optimised pharmacotherapy.
Together, the results of the studies described in this thesis contribute to the discussion of the possibility of extrapolation of results between animals and humans and between children and adults.