Sink physically-maintained

In PAMPA measurements each well is usually a one-point-in-time (single-timepoint) sample. By contrast, in the conventional multitimepoint Caco-2 assay, the acceptor solution is frequently replaced with fresh buffer solution so that the solution in contact with the membrane contains no more than a few percent of the total sample concentration at any time. This condition can be called a physically maintained sink. Under pseudo-steady state (when a practically linear solute concentration gradient is established in the membrane phase see Chapter 2), lipophilic molecules will distribute into the cell monolayer in accordance with the effective membrane-buffer partition coefficient, even when the acceptor solution contains nearly zero sample concentration (due to the physical sink). If the physical sink is maintained indefinitely, then eventually, all of the sample will be depleted from both the donor and membrane compartments, as the flux approaches zero (Chapter 2). In conventional Caco-2 data analysis, a very simple equation [Eq. (7.10) or (7.11)] is used to calculate the permeability coefficient. But when combinatorial (i.e., lipophilic) compounds are screened, this equation is often invalid, since a considerable portion of the molecules partitions into the membrane phase during the multitimepoint measurements. 

In this chapter we use the term sink to mean any process that can significantly lower the concentration of the neutral form of the sample molecule in the acceptor compartment. Under the right conditions, the ionization and the binding sinks serve the same purpose as the physically maintained sink often used in Caco-2 measurements. We will develop several transport models to cover these chemical sink conditions. When both of the chemical sink conditions (ionization and binding) are imposed, we will use the term double sink in this chapter. 

Fig. 5), the vaginal uptake of both alkanols and alka-noic acids also follows a first-order rate process and is dependent on the drug concentration in the vaginal fluid. The results agree well with a physical model that has a hydrodynamic diffusion layer in series with the mucosal membrane, that consists of two parallel pathways a lipoidal pathway and an aqueous pore pathway (Fig. 6). Immediately behind the mucosa (serosal side) a perfect sink is maintained by hemoperfusion. 

Physically-maintained sink conditions In cell-based assays, an aliquot is removed for analysis from the receiver wells to make time point measurements. This is replicated in Caco-2 but not in PAMPA. 

Representation of the density n(r) [or, effectively, the electrostatic potential — 0(r)] near any one of the sinks as an expansion in the monopole and dipole contribution only [as in eqn. (230c)] is generally, unsatisfactory. This is precisely the region where the higher multipole moments make their greatest contribution. However, the situation can be improved considerably. Felderhof and Deutch [25] suggested that the physical size of the sinks and dipoles be reduced from R to effectively zero, but that the magnitude of all the monopoles and dipoles, p/, are maintained, by the definition... 

As already mentioned all chemical and physical processes result in a change in heat. Depending on whether the process is endothermic or exothermic, heat will flow from, or to, the heat sink in order to maintain isothermal conditions. This heat... 

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