Diffusion membrane-bound drugs

Figure 22.1 Nanoparticulate-mediated drug delivery across the tight (a) and leaky (b) tissue barriers. In the case of nanocrystals and drug solubilization systems, the dissolution rate is increased and free drug permeates across the tissue barrier with the appropriate mechanism. The nanoparticulate-bound drug behaves differently. The nanoparticulates are too large for the direct transcellular permeation across the cells walls (I), for the paracellular diffusion through the tight tissue boundaries (a-l I), and for the active transport by membrane transporters...

As already noted, nearly all the diuretics in common use exert their effects from within the lumen of the nephron. These drugs are in general highly protein-bound and are not filtered by the glomerulus. Instead, in common with many other drugs and organic molecules, they diffuse from the peritubular vasculature across the basolateral membrane of the proximal tubular cells and from there are actively secreted into the filtrate. The efficacy of a diuretic depends not only on the mass and rate of delivery of drug to the filtrate but also on the body s state of sodium and water homeostasis. 

Within the blood, drug is dissolved in the plasma water (unbound concentration, Cu). Drug can also be bound to plasma proteins and concentrated in the red blood cells. It is the unbound drug molecules that diffuse across the membranes into the tissues. At equilibrium, the unbound concentration of drug is thought to be the same throughout the whole body. 

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