Transport kinetics, bodies

Figure 8.4 The results of two experiments designed to determine the relative degree to which transdermal nitroglycerin systems control delivery into the body. In left panel, drug release from the patch into an aqueous receptor is measured ( Experiment A ). In the right panel ( Experiment B ) the transport kinetics are re-assessed when excised skin is interposed between the patch and the receiving medium (Modified from Hadgraft J. etal , Int. J.Pharm., 73 (1991) 125-130)...

Physical transfer processes include evaporation and precipitation, and also membrane diffusion as a basic mechanism of element transfer in the human body. A difference in diffusion rates between isotopes inevitably results in their fractionation over the course of element transport (kinetic isotope fractionation effect). When an element undergoes a chemical reaction, this can also be described as an element transfer process from one element species into another. Again, if reaction rates between isotopologs differ, this gives rise to a difference in isotopic... 

Nonetheless, these methods only estimate organ-averaged radiation dose. Any process which results in high concentrations of radioactivity in organs outside the MIRD tables or in very small volumes within an organ can result in significant error. In addition, the kinetic behavior of materials in the body can have a dramatic effect on radiation dose and models of material transport are constandy refined. Thus radiation dosimetry remains an area of significant research activity. 

WASP/TOXIWASP/WASTOX. The Water Quality Analysis Simulation Program (WASP, 3)is a generalized finite-difference code designed to accept user-specified kinetic models as subroutines. It can be applied to one, two, and three-dimensional descriptions of water bodies, and process models can be structured to include linear and non-linear kinetics. Two versions of WASP designed specifically for synthetic organic chemicals exist at this time. TOXIWASP (54) was developed at the Athens Environmental Research Laboratory of U.S. E.P.A. WASTOX (55) was developed at HydroQual, with participation from the group responsible for WASP. Both codes include process models for hydrolysis, biolysis, oxidations, volatilization, and photolysis. Both treat sorption/desorption as local equilibria. These codes allow the user to specify either constant or time-variable transport and reaction processes. 

Several kinetic parameters can be measured on different experimental systems to account for the interaction of a compound with CYPs. For example when studying the metabolic stability of a compound, it could be measured in a recombinant CYP system, in human liver microsomes, in hepatocytes and so on. Each system increases in biological complexity. Although in the recombinant CYP system only the cytochrome under consideration is studied, in the case of the human liver microsomes, there is a pool of enzyme present that includes several CYPs, and finally in the hepatocyte cell system, metabolizing enzymes play an important role in the metabolic compound stability. In addition, transport systems are also present that could involve recirculation or other transport phenomena. The more complex the experimental system, the more difficult it is to extract information on the protein/ligand interaction, albeit it is closer to the in vivo real situation and therefore to the mechanism that is actually working in the body. 

For a drug to interact with a target, it has to be present in sufficient concentration in the fluid medium surrounding the cells with receptors. Pharmacokinetics (PK) is the study of the kinetics of absorption, distribution, metabolism, and excretion (ADME) of drugs. It analyzes the way the human body deals with a drug after it has been administered, and the transportation of the drug to the specihc site for drug-receptor interaction. For example, a person has a headache and takes an aspirin to abate the pain. How does the aspirin travel from our mouth to reach the site in the brain where the headache is and act to reduce the pain ... 

The driving force of the transport of salts, proteins, etc., through the cell membrane from the nuclens to the body fluids, and vice versa, is a complicated biochemical process. As far as is known, this field has not been explored by traditional solution chemists, although a detailed analysis of these transfer processes indicates many similarities with solvent extraction processes (equilibrium as well as kinetics). It is possible that studies of such simpler model systems could contribute to the understanding of the more complicated biochemical processes. 

After the formulation of defect thermodynamics, it is necessary to understand the nature of rate constants and transport coefficients in order to make practical use of irreversible thermodynamics in solid state kinetics. Even the individual jump of a vacancy is a complicated many-body problem involving, in principle, the lattice dynamics of the whole crystal and the coupling with the motion of all other atomic structure elements. Predictions can be made by simulations, but the relevant methods (e.g., molecular dynamics, MD, calculations) can still be applied only in very simple situations. What are the limits of linear transport theory and under what conditions do the (local) rate constants and transport coefficients cease to be functions of state When do they begin to depend not only on local thermodynamic parameters, but on driving forces (potential gradients) as well Various relaxation processes give the answer to these questions and are treated in depth later. 

In 1937, dost presented in his book on diffusion and chemical reactions in solids [W. lost (1937)] the first overview and quantitative discussion of solid state reaction kinetics based on the Frenkel-Wagner-Sehottky point defect thermodynamics and linear transport theory. Although metallic systems were included in the discussion, the main body of this monograph was concerned with ionic crystals. There was good reason for this preferential elaboration on kinetic concepts with ionic crystals. Firstly, one can exert, forces on the structure elements of ionic crystals by the application of an electrical field. Secondly, a current of 1 mA over a duration of 1 s (= 1 mC, easy to measure, at that time) corresponds to only 1(K8 moles of transported matter in the form of ions. Seen in retrospect, it is amazing how fast the understanding of diffusion and of chemical reactions in the solid state took place after the fundamental and appropriate concepts were established at about 1930, especially in metallurgy, ceramics, and related areas. 

The kinetic transport mechanisms that permit sintering are solid-state processes, and therefore sintering is an important forming process that does not require melting. Materials with high melting temperatures, such as ceramics, can be molded into a complex shape from a powder and subsequently sintered into a solid body.13... 

In the physiological sense, one can divide the body into compartments that represent discrete parts of the whole-blood, liver, urine, and so on, or use a mathematical model describing the process as a composite that pools together parts of tissues involved in distribution and bioactivation. Usually pharmacokinetic compartments have no anatomical or physiological identity they represent all locations within the body that have similar characteristics relative to the transport rates of the particular toxicant. Simple first-order kinetics is usually accepted to describe individual... 

---