@article {Glassmanjpet.119.257113, author = {Patrick M. Glassman and Vladimir R. Muzykantov}, title = {Pharmacokinetics, Biodistribution, and Pharmacodynamics of Drug Delivery Systems}, elocation-id = {jpet.119.257113}, year = {2019}, doi = {10.1124/jpet.119.257113}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The use of drug delivery systems (DDSs) is an attractive approach to facilitate uptake of therapeutic agents at the desired site of action, particularly when free drug has poor pharmacokinetics/biodistribution (PK/BD) or significant off-site toxicities. Successful translation of DDSs into the clinic is dependent on a thorough understanding of the in vivo behavior of the carrier, which has for the most part been an elusive goal. This is, at least in part, due to significant differences in the mechanisms controlling pharmacokinetics for classical drugs and DDSs. In this review, we summarize the key physiological mechanisms controlling the in vivo behavior of DDSs, comparing and contrasting this with classical drugs, and describing engineering strategies designed to improve DDS PK/BD. In addition, we describe quantitative approaches that could be useful for describing PK/BD of DDSs, as well as critical steps between tissue uptake and pharmacologic effect.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/early/2019/03/05/jpet.119.257113}, eprint = {https://jpet.aspetjournals.org/content/early/2019/03/05/jpet.119.257113.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }