The Utility Of Pharmacometrics In Drug Development And Pharmacotherapy Of Antimicrobials

University of Minnesota Ph.D. dissertation. December 2017. Major: Experimental & Clinical Pharmacology. Advisors: Richard Brundage, Marnie Peterson. 1 computer file (PDF); xiii, 169 pages.Infectious diseases are a growing major public health concern due to the increase of antimicrobial resistance to current therapies and the lack of new drugs in development. As an alternative to developing new anti-infective drugs, my thesis research focuses on ways to optimize current antimicrobial therapies. This thesis aims specifically to utilize pharmacometric modeling and simulation that applies pharmacokinetic (PK) and pharmacodynamics (PD) principles to provide insights into ways to maximize drug effect while minimizing side effects and preventing resistance. Mathematical and statistical methods are used to develop integrated drug, body, and microbial models that quantify relationships among dose, plasma and tissue concentrations, and microbial killing. These pharmacometric models are then used to predict the outcome of various untested scenarios to select the optimal dosing regimens for confirmatory clinical testing