Metabolism (in vitro)
Studies of drug metabolism by using microsomes is the longest used method within the PK-group. Both human liver microsomes, that expresses all enzymes which are available in a human liver, as well as microsomes that only expresses specific CYP enzymes, such as CYP3A4 and CYP2D6 are used. With these methods we are able to investigate which enzymes that are responsible for the metabolism of different drugs and also which other substances that might affect these processes.
Transport (in vitro)
Until now our studies have primarily been restricted to investigation of OATP1B1 mediate drug transport by using overexpressed HEK297 cells.
In collaboration with AstraZeneca in Mölndal, and Cellartis in Gothenburg, Sweden, we are currently looking into alternative methodologies. Both primary hepatocytes as well as human embryonic stem cells are being tested in this project which is supported by grants from NordForsk and NFR. Also other cell lines are being tested and the cells are tested in 2D systems as well as in bioreactors.
In 2005 the group started to work with pharmacokinetic population modelling as well as in vitro-in vivo extrapolation. NONMEM is mainly used for the population modeling while SimCYP is the preferred program for the in vitro-in vivo extrapolation studies.
Together with our clinical collaborating partners we have performed several pharmacokinetic interaction studies. Most of these studies have focused on the interactions between immunosuppressive drugs and other drugs used by solid organ transplant recipients. In addition to being important in the change of the care of these patients we have taken these hypothesis further to investigate the basal mechanism involved in the interactions. We have also developed new analytical methods in order to be able to measure drug concentrations at the site of action. For immunosuppressive drugs, which exerts its effect inside T-lymphocytes and some major side-effects in the kidneys, we have developed methods to measure the cyclosporine concentrations both within T-lymphocytes as well as in renal tissue.
Patient populations especially investigated are:
- Solid organ transplant recipients
- Patients using psychotropic drugs
- Morbidly obese patients going through bariatric surgery
- Patients with elevated cholesterol levels using statins