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Drug Metabolism and Pharmacokinetics

The drug metabolism and pharmacokinetics (DMPK) group ensures that novel therapeutics developed by IACS scientists are safe, effective and stable enough to be dosed to humans. To be therapeutically effective, a drug must reach the protein target in the tumor for a sufficient amount of time and at a specific concentration. A drug’s journey generally begins in the stomach where it arrives after being swallowed and subsequently gets absorbed from the gastro-intestinal tract. A drug must have properties that promote stable circulation in the blood, prevent degradation by metabolic enzymes present in the body (most notably the liver) and prevent elimination by efflux transporters. Once the drug has reached the site of action within the tumor, the compound must cross the cell membrane to engage the protein of interest.

Besides examining the pharmacokinetic properties of new agents, DMPK scientists also ensure that no drug-drug interactions occur. Drug interactions can influence pharmacokinetics of other co-adminstered agents either increasing exposure(which can lead to toxicity) or by accelerating metabolism of a second agent (making it ineffective).

To ensure that candidate drug compounds have all the necessary properties to become an approved drug, researchers use a variety of high-throughput in vitro, as well as limited in vivo preclinical studies, which track drug levels using sophisticated analytical chemistry and mass spectroscopy techniques.

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