Question

Lipophilic drugs are not readily eliminated through renal excretion. What chemical property is altered through metabolism that allows elimination through the renal pathway?

Answer 1

Ans) Lipophilic drugs must be biotransformed to hydrophilic drug metabolites to be excreted. Drug may be excreted via a number of routes, such as the kidney or in bile, sweat, and breast milk. The lungs are an excretion route by which volatile lipophilic substances (e.g., inhaled general anesthetics) can be excreted. Changes in excretion rates will affect the plasma concentration of drugs and their metabolites and thus play an important role in the design of drug regimens.

- Pulmonary excretion is important for gaseous lipophilic substances. The gaseous general anesthetics are the most common example. Drug diffuses from the plasma into the alveolar space and is excreted during expiration.

Excretion via Breast Milk
Breast milk is a quantitatively relatively minor route of drug excretion. Nevertheless, it is clinically important for breastfeeding mothers and their infants. The baby will ingest drugs excreted in the breast milk. Moreover, breast milk has a lower pH than plasma. Accordingly, basic drugs will be concentrated in the breast milk through the phenomenon of ion (pH) trapping. A number of drugs can reach clinically significant concentrations in the breast milk and thereby affect nursing babies.

- The kidney is the major organ for drug excretion. Lipophilic drug molecules are not directly excreted from the kidney. Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine. Drugs and their metabolites are also excreted into bile.