Clinical pharmacology

Personalized treatment of pancreatic cancer through monitoring of gemcitabine and endogenous nucleotides.

Bjånes, Kamceva, Schjøtt and Riedel with collaborators.

Pancreatic cancer (PDAC) affects 300 000 patients worldwide/year with a five year survival of 5%. The nucleoside analogue gemcitabine is the most prevalent chemotherapeutic agent in the treatment of PDAC. Gemcitabine can be combined with other cytotoxic drugs and adjuvant interventions to enhance anti-cancer effect. In this project, an in vitro model with resistant PDAC-cells in culture is used to study changes in transport, metabolism and effect of gemcitabine and metabolites. Use of ultrasound and microbubbles (sonoporation) are expected to increase cellular uptake of gemcitabine. Quantification of gemcitabine and metabolites, including targets like endogenous nucleotides, are possible through the group’s development of several mass spectrometry methods. Use of enzyme-inhibitors of important gemcitabine-resistance mechanisms will be assessed in the studies, and the main research motivation is to gain knowledge of effective treatment of PDAC-patients. For further information on this project contact Tormod Bjånes (tormod.karlsen.bjanes@helse-bergen.no).

Therapeutic drug monitoring of new anticoagulants in geriatric medicine.

Stokes, Riedel and Schjøtt with collaborators.

The group of new oral anticoagulants now termed direct oral anticoagulants or DOACs including dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Atrial fibrillation is an important risk factor for embolic stroke in patients older than 80 years. Among patients older than 75 year, 10% of the population has atrial fibrillation. Knowledge of correct dosing and monitoring of DOACs in older patients is lacking. Older patients represent a risk group with regard to adverse effects of DOACs. The main research question is to study if pharmacological and biochemical monitoring of DOACs provide safer pharmacotherapy among nursing home patients. The project includes a survey of prescribing of DOACs in nursing homes with regard to clinical, pharmacological and biochemical characteristics. Furthermore, studies include evaluation of dose-related inter- and intraindividual variation in DOAC-concentrations measured with mass spectrometry methods. The significance of pharmacogenetics and drug interactions for this variation will be explored. For further information on this project contact Charlotte Stokes (charlotte.lorentze.stokes@helse-bergen.no).