Distribution

Distribution in elderly

Changes in drug distribution are theoretically due to alterations in body composition and serum protein binding. Regarding body composition, elderly do have decreased lean body mass and decreased total body water. The contribution of fat tissue to the total body composition is increased. The clinical importance is a reduction of the half-lives of water-soluble drugs (digoxin, ethanol, ciprofloxacin, antipyrine, and cimetidine), since their distribution volume is reduced. Conversely, lipophilic drugs (benzodiazepines, tolbutamide) exhibit an increase in distribution volume and half-life.

 

Another important issue for the distribution of drugs is the serum binding-protein concentration. This concentration tends to fall in elderly. For a strongly bound drug with a narrow therapeutic window (e.g. phenytoin (fenytoine) at 95%), a small reduction in binding protein level (and thus percentage bound drug; e.g. 90%) could lead to doubled free drug concentration (from 5% to 10%). However, the clinical significance of falling serum protein levels on drug concentrations cannot be determined very easily, because higher free drug concentrations are better available for metabolism and subsequent elimination.

1

Distribution to peripheral tissues is poor due to:

2

Would an elderly patient with an intramuscular shot of a lipophilic drug have a shorter or longer duration of action compared to a younger patient?