Hans Prydz Guest Lecture by Pia Abel zur Wiesch
Pia Abel zur Wiesch at the Institute of Pharmacy, UiT The Arctic University of Norway is heading the Systems Pharmacology group that uses theoretical models in close collaboration with experimentalists and clinicians to explore how we could use both within-host and population-wide drug treatment strategies to minimize human morbidity and mortality. The group is focusing on bacterial population dynamics, specifically pathogen population dynamics of anti-infective therapy. Pia Abel zur Wiesch in addition holds a visiting professorship at Yale School of Public Health. The title of her talk is "How to design drug dosing strategies: at the interface of chemical kinetics and population biology".
Pia Abel zur Wiesch (Photo: Univ of Tromsø)
Optimizing treatment strategies for TB
In this era of rising concerns about antibiotic resistance, the rational design of optimal antibiotic treatment regimens remains an important unrealized goal. Currently, the characteristics of antibiotic treatment regimens (e.g. dosing levels, treatment duration, route of administration) are determined largely based on costly in vivo experiments. The sheer number of possible dosing strategies that must be tested contributes to the delay and cost of the development of new drugs and may limit the feasibility of finding optimal regimen characteristics.
To predict optimal dosing and thereby accelerate the design of treatment strategies, we developed a modeling framework that integrates bacterial population biology with the intracellular reaction kinetics of antibiotic-target binding (Abel zur Wiesch et al., Science Translational Medicine 2015).
Here, we demonstrate how modeling the chemical kinetics of drug-target binding can identify the best time-concentration profile of antibiotics. We find that the physicochemical characteristics of drug-target binding are sufficient to explain the pharmacodynamics of commonly used antibiotics. In practical terms, our models can be used as a tool in the rational design of treatment for bacterial infections, thereby shortening the time to new drugs as well as improving treatment with existing antibiotics. Because of the generality of drug-target binding kinetics, these approaches can also be adapted to other diseases where the effects of physiological fluctuations of drug concentration are also poorly understood, such as HIV, malaria and cancer.