Modeling kinetics of subcellular disposition of chemicals.
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. firstname.lastname@example.orgShow MeSH
Mentions: The disposition of chemicals in animals and humans has been studied mainly in relation to chemotherapy. The history of classical pharmacokinetics is summarized in Figure 12, and more details are given in the following text. The notion of a relationship between an anesthetic effect and the concentration of ether in the brain dates back to the middle of the 19th century.(2037) The kinetics of disposition of chemicals has been studied quantitatively in animals and humans and documented since the second decade of the 20th century.2038–2048 During the same time period, the Michaelis−Menten description of saturable kinetics(2049) and the one-compartment model(2050) were developed. The 1930s brought the two-compartment models(2051) and the key concepts of the mean residence time,(2052) clearance,2053,2054 and the volume of distribution.(2055) The one-compartment model and two-compartment models were later applied to the disposition kinetics of drugs2056–2058 and radioactive substances2059–2064 in the organisms. Since the 1950s, kinetic models of multiple dosage regimens2056,2065–2068 have had a broad impact on how therapeutic interventions are performed. The research area was called pharmacokinetics(2058) and developed(2013) into a key pharmacy discipline(75) that is taught in all pharmacy programs around the world. More-detailed descriptions of the fates of chemicals in the body, the PBPK models, were spearheaded by physiologists, who routinely monitored the blood flows and the concentrations of oxygen, carbon dioxide, and anesthetic gases in individual organs.(2069) The compartments in PBPK models are individual organs or their specified sets, in contrast to the models of classical pharmacokinetics, which utilize loosely defined compartments, the number and function of which is dictated by the fit of the model to the data. Principles of PBPK modeling were formulated in the 1960s.2070–2073
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. email@example.com