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John Clarke Lab Xenobiotic Exposures and Toxicities

Precision Medicine Research

This project investigates how perturbations in two or more factors in drug absorption, distribution, metabolism, and excretion (ADME) affect drug exposures and toxicities. Results from this work will help to inform clinicians, drug companies and regulators regarding at-risk populations for drug toxicities.

Natural Product x disease Environment-Drug Interaction

A simplistic representation of a multifactorial interaction on pharmacokinetics and the risk of toxicity. Liver disease can decrease the expression and function of hepatic uptake transporters (top right square) and potentially increase systemic drug exposure and the risk of concentration-dependent adverse events. Natural product constituents can inhibit drug uptake (bottom left square and IC50 graph on left). The combination of both factors can cause an additive effect on drug pharmacokinetics resulting in the greatest increase in systemic exposure in liver disease patient self-medicating with over-the-counter dietary supplements (bottom right square and plasma drug concentration time course on right).