Excretion In Other Body Fluids

Sweat and Saliva

Excretion of drugs into sweat and saliva occurs but has only minor importance for most drugs. The mechanisms involved in drug excretion are similar for sweat and saliva. Excretion mainly depends on the diffusion of the un-ionized lipid-soluble form of the drug across the epithelial cells of the glands. Thus, the pKa of the drug and the pH of the individual secretion formed in the glands are important determinants of the total quantity of drug appearing in the particular body fluid. It is not definitely established whether active drug transport occurs across the ducts of the glands.

Lipid-insoluble compounds, such as urea and glyc-erol, enter saliva and sweat at rates proportional to their molecular weight, presumably because of filtration through the aqueous channels in the secretory cell membrane. Drugs or their metabolites that are excreted into sweat may be at least partially responsible for the dermatitis and other skin reactions caused by some therapeutic agents. Substances excreted into saliva are usually swallowed, and therefore their fate is the same as that of orally administered drugs (unless expectoration is a major characteristic of a person's habits). The excretion of a drug into saliva accounts for the drug taste patients sometimes report after certain compounds are given intravenously.

Milk

Many drugs in a nursing mother's blood are detectable in her milk (Table 4.7). The ultimate concentration of the individual compound in milk will depend on many factors, including the amount of drug in the maternal blood, its lipid solubility, its degree of ionization, and the extent of its active excretion. Thus, the physico-chemical properties that govern the excretion of drugs into saliva and sweat also apply to the passage of drugs into milk.

Since milk is more acidic (pH 6.5) than plasma, basic compounds (e.g., alkaloids, such as morphine and codeine) may be somewhat more concentrated in this fluid. In contrast, the levels of weak organic acids will probably be lower than those in plasma. In general, a high maternal plasma protein binding of drug will be associ-

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