Lipid solubility, antimicrobial drug

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... 

From an in vitro perspective, solubility in water and in organic solvents determines the choice of solvent, which, in turn, influences the choice of extraction procedure and analytical method. Solubility can also indirecfly impact the timeframe of an assay for compounds that are unstable in solution. From an in vivo perspective, the solubility of a compound influences its absorption, distribution, metabolism, and excretion. Both water solubility and lipid solubility are necessary for the absorption of orally administered antimicrobial drugs from the gastrointestinal tract. This is an important consideration when selecting a pharmaceutical salt during formulation development. Lipid solubility is necessary for passive diffusion of drugs in the distributive phase, whereas water solubility is critical for the excretion of antimicrobial drugs and/or their metabolites by the kidneys. 

TABLE 2.2 Influence of Lipid Solubility of Antimicrobial Drugs on Pharmacokinetic Properties (ADME) ... 

Many chemicals are more soluble in lipids than in water. The lipid layer of the stratum corneum will dissolve and can absorb chemicals placed on the surface of the skin. In fact, this characteristic is important in transdermal delivery of drugs, for example, the skin patch for drug delivery, and in what has been termed substantivity or persistence of the applied antimicrobial. 

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