Lipid solubility of drugs

The ability of the anesthetic agent to function is related to the partial pressure of the drug in the brain. Two major factors dictate the concentration of anesthetic agent in the neural tissue (1) the pressure gradients from lung alveoli to the brain (i.e., inhaled gas —> alveoli — bloodstream —> brain) and (2) the lipid solubility of the drug that enables it to pass between the blood-brain barrier to the central nervous system. 

The basic concept behind studies such as this is that esterification may modify corticosteroid activity by (1) increasing lipid solubility of the drug and thereby... 

Natural alkaloids and most tertiary antimuscarinic drugs are well absorbed from the gut and conjunctival membranes. When applied in a suitable vehicle, some (eg, scopolamine) are even absorbed across the skin (transdermal route). In contrast, only 10-30% of a dose of a quaternary antimuscarinic drug is absorbed after oral administration, reflecting the decreased lipid solubility of the charged molecule. 

Health hazards from drug residues in food depend on the frequency and degree of human exposure. Increase in the degree of human exposure occurs when injection sites are accidentally consumed. Continuous exposure is more probable when a side or quarter of a contaminated food animal is purchased by a consumer for deep-freeze use. Basic antibiotics such as chloramphenicol, erythromycin, tylosin, and oleandomycin, are more likely to accumulate in tissue at a higher concentration than in plasma due both to ion trapping, which results from a pH difference between blood and tissue, and to the innate lipid solubility of the compounds (1). A factor with the potential to reduce the drug residues intake is that most animal tissues are cooked before eating, which may decrease 269... 

The partition coefficient, which will be described in more detail later in this chapter, is the relative solubility of the compound in lipid and water, and the compound s solubility really reflects the ability of the toxicant to move from a relatively aqueous environment across a lipid membrane. It is this factor that is often manipulated in pesticide and drug formulations to create a vehicle. Membrane permeability is therefore strongly correlated to the lipid solubility of the toxicant in the membrane as well as... 

The preferred route of administration in Western countries is by smoking. The high lipid solubility of the drug leads to extensive sequestration in the lipid compartments of the body, and metabolites may be excreted for as long as a week after a single dose. 

The relative solubilities of drugs in the aqueous media and lipid tissues of the body play a major part in their absorption and transport to their sites of action. 

Factors that can affect bioavailability include metabolism (to be discussed in more detail in Chapter 3), lipid solubility of the drug, chemical stability of the drug (e.g., penicillin G is unstable at gastric pFI), and the nature of the drug formulation (i.e., particle size, salt form, presence of inert binders, etc.). 

It was at the turn of the twentieth century that the importance of lipid solubility in drug action was also independently described by Meyer and Overton (the significance of the oil/water partition coefficient was discussed in Chapter 2). The importance of lipid solubility in drug action subsequently became manifested in the lipoid theory of cellular depression. In essence, this theory correlated a pharmacological effect (e.g., CNS depression) with a physical property (i.e., lipid solubility) rather than a structure-activity relationship. In the process, the theory was attempting to explain the diverse chemical structures that exist within the hypnotic and general anesthetic classes of drugs (see Chapter 11). Today, we realize the limitations of the lipoid theory and appreciate that the distinction between physical and chemical factors is illusory, since chemical structure is a determinant of physical properties. 

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