About the project
Dosing immunosuppressive drugs is challenging due to large inter- and intra-individual variability in its pharmacokinetics in combination with and narrow therapeutic windows where small differences in blood drug concentrations may lead to therapeutic failures and/or serious adverse drug reactions. Improved personalized and tailored immunosuppression monitoring strategies has been stated as the most important, modifiable factor to improve long-term patient and graft outcomes following renal transplantation. Unfortunately, despite the application of advanced computer tools, we still cannot explain approximately 30-40% of the pharmacokinetic variability of the immunosuppressive drugs. An almost unexplored source of variability in drug disposition is the community of microorganisms in our gut. The gut microbiome may affect drugs either directly by chemical transformation, or indirectly through interacting with the host’s drug metabolism or transport systems. Emerging evidence implies an extensive role of gut microbiota in modulating the toxicity and systemic exposure of certain drugs. However, the effects of the gut microbiome on immunosuppressive drugs and vice versa remain unclear.
The current project will combine information from in vitro experiments, unique clinical data from a clinical trial at Oslo University Hospital and advanced computational modelling to improve our understanding of the complex host-microbiome-drug interplay that makes dosing immunosuppressive drugs such a challenge. Our results will be a novel and important part of improved personalized medicine for solid organ transplant recipients.
The current project meets the sustainable development goal number 3 from the United Nations: “Ensuring healthy lives and promoting well-being for all at all ages” as it aims to uncover the complex interactions between the gut microbiome and immunosuppressive drugs which is a target with a high potential to improve health outcomes for patients with kidney failure.