Aston-Derks paper accepted in J Math Biology

The paper “A mathematical analysis of rebound in a target-mediated drug disposition model. I. without feedback” by Philip Aston and Gianne Derks (in collaboration with Balaji Agoram and Piet van der Graaf at Pfizer) has been accepted for publication in the Journal of Mathematical Biology.  In the paper, they consider the possibility of free receptor (antigen/cytokine) levels rebounding to higher than the baseline level after one or more applications of an antibody drug using a target-mediated drug disposition model. Using geometry and dynamical systems analysis, it is shown that rebound will occur if and only if the elimination rate of the drug-receptor product is slower than the elimination rates of the drug and of the receptor. Also analysed is the magnitude of rebound through approximations and simulations and it is demonstrated that it increases if the drug dose increases or if the difference between the elimination rate of the drug-receptor product and the minimum of the elimination rates of the drug and of the receptor increases.  The paper appears online here.