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Patrik Lundquist
Uppsala University

Dr. Patrik Lundquist is a senior scientist at the Department of Pharmacy, Uppsala University, Sweden. He has a long-standing research interest in drug Absorption, Distribution, Metabolism, and Excretion (ADME) which he has studied both in academic and industrial settings. The group´s focus is on the interplay of transporters and metabolizing enzymes in the epithelial cells of the intestine and liver and their effects on the systemic and intracellular exposure of drugs and other organic molecules in man. To this end, the team has developed several state-of-the-art cell and tissue-based in vitro methods that can be utilized to assess human oral exposure without the need for animal experimentation. These methods are currently being implemented in the RISK-HUNT3R consortium.

Open Tox 2023 Virtual Conference

In vitro determination of metabolism and permeability to predict human oral exposure

Oral bioavailability in man is defined as the fraction of the given dose reaching the systemic circulation. The bioavailability is a function of processes generally grouped under the acronym ADME, Absorption, Distribution, Metabolism, and Elimination taking place in mainly the epitheliums of the small intestine, liver and kidney. It has long been realized that animal experiments poorly predicts human bioavailability and systemic exposure. In the pharmaceutical industry cell and tissue based in vitro tools to study ADME processes along with advances in physiology-based pharmacokinetic modeling (PBPK) has improved our understanding of human exposure. Today it is uncommon that the ADME properties of a new drug candidate is the cause of failure of a drug project when the new drug candidate is advanced into human patients. Using methods to assess the intracellular free concentrations the potential for interactions with intracellular effector targets can be assessed. This presentation will focus on in vitro ADME methods to determine systemic and intracellular oral exposure in men.