Translational aspects of brain drug distribution in health and disease

The interpretation and translation of neuropharmacokinetic data might be even more challenging during disease conditions, where a disrupted integrity and function of the BBB may be present.

Recent findings point towards dysfunctional BBB as being the cause of neurodegenerative disease etiology and progression. As a result, this might lead to altered brain pharmacokinetics of CNS drugs as well as peripherally acting drugs, which normally have a very low brain penetrance, resulting in unpredicted CNS effect or side effect profiles. Moreover, CNS disorder pathology usually affects certain areas of the brain, which might result in regional differences of brain drug distribution and binding.

Hence, our research aims to investigate differences in drug distribution to and within the brain as well as drug binding in separate brain regions both in health and disease, preclinically and clinically. By combining and comparing in vitro and in vivo experiments with clinical studies, the current project strives to increase the understanding of pharmacokinetics and disease implication on brain drug distribution, thereby improving treatment of patients in the clinic. Results from in vitro techniques as well as microdialysis and non-invasive imaging techniques, such as positron emission tomography (PET), is integrated and used to address the current issues.

Investigators: Irena Loryan and Margareta Hammarlund-Udenaes in collaboration with Stina Syvänen (Dept Public Health and Caring Sci).