Drug distribution passive diffusion

The mathematical description of drug distribution is in its classical form based on a concept considering the body as a single unit separated from the environment by a membrane permeable to drugs by passive diffusion in which the drug is distributed homogeneously. Such a view permits the use of equation (3). 

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

In order to design such an efficient and effective device, one must understand the mechanisms by which drug is transported in the ocular interior. One issue debated in the literature for some time has been the relative importance of transport by passive diffusion versus that facilitated by the flow of fluid in the vitreous (see, e.g., Ref. 226). To predict the geometric distribution even at steady state of drug released from an implant or an intravitreal injection, one must appreciate which of these mechanisms is at work or, as appropriate, their relative balance. 

Unchanged passive diffusion and no change in bioavailability for most drugs l Active transport and i bioavailability for some drugs l First-pass extraction and T bioavailability for some drugs i Volume of distribution and T plasma concentration of water-soluble drugs T Volume of distribution and T terminal disposition half-life (t ) for fat-soluble drugs... 

The transport mechanisms that operate in distribution and elimination processes of drugs, drug-carrier conjugates and pro-drugs include convective transport (for example, by blood flow), passive diffusion, facilitated diffusion and active transport by carrier proteins, and, in the case of macromolecules, endocytosis. The kinetics of the particular transport processes depend on the mechanism involved. For example, convective transport is governed by fluid flow and passive diffusion is governed by the concentration gradient, whereas facilitated diffusion, active transport and endocytosis obey saturable MichaeUs-Menten kinetics. 

The unbound drug in the systemic circulation is available to distribute extravascularly. The extent of distribution is mainly determined by lipid solubility and, for weak organic acids and bases, is influenced by the pK3/pH-dependent degree of ionization because only the more lipid-soluble non-ionized form can passively diffuse through cell membranes and penetrate cellular barriers such as those which separate blood from transcellular fluids (cerebrospinal and synovial fluids and aqueous humour). The milk-to-plasma equilibrium concentration ratio of an antimicrobial agent provides a reasonably... 

Pharmacokinetics is now challenged by the growing importance of transporters, a relatively new and potentially major factor in drug absorption, distribution, metabolism and excretion (the ADME process). Several years ago, passive diffusion was the main advanced process by which xenobi-otics were believed to move through body membranes. The... 

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