Autumn McKnite – AFPE Fellowship Recipient
Department of Pharmacology & Toxicology, Dr. Kevin Watt’s lab
My research focuses on the pharmacokinetics of five drugs (amlodipine, fentanyl, fluconazole, methylprednisolone and midazolam) commonly used in critically ill children on continuous renal replacement therapy (CRRT). We use a combination of ex vivo and in vivo studies to develop physiologically based pharmacokinetic models (PBPK) that include drug-drug and drug-circuit interactions. PBPK models represent the body as a set of virtual organ compartments linked by blood flow. Mathematical equations characterize changes in drug concentrations as the drug passes through the virtual organs. These can account for the impact of physiologic covariates such as age and disease, as well as the impact of CRRT by using an additional compartment to represent the circuit. Once setup, the model is validated and refined using empirical drug concentration data from children who are on CRRT and receiving one or more of the study drugs. Validated models can be used to predict optimal dosing under different scenarios, e.g. drug co-administration and different CRRT settings. The results of this research have the potential to enhance our understanding of how critical illness influences drug disposition and action in the developing child, as well as improving dosing recommendations in this vulnerable population.