Following oral administration, most drugs dissolve in the stomach. Little absorption takes place here due to the small surface area and low pH, which means that drugs which are weak bases are in an ionized state. Absorption primarily takes place in the small intestine because of the large surface area and high pH, which favours the unionised state of most drugs. With increasing age a number of changes occur in the gastrointestinal tract which should make the rate of absorption less predictable, including a reduction in acid secretion in the stomach, decreased gastric emptying, diminished splanchnic blood flow and decreased gastrointestinal mobility (Geokas and Haverback, 1969; Evans et al., 1981; Greenblatt et al., 1982; Goldberg and Roberts, 1983; Montamat et al., 1989; Woodhouse, 1994). However, in practice few drugs have significantly delayed rates of absorption (Greenblatt et al., 1982; Woodhouse, 1994). This is probably because potentially rate-limiting factors in the small intestine (such as surface area and lumenal pH) are not altered to a critical degree.
Once drugs are absorbed from the gut, they enter the portal circulation and must pass through the liver before entering the systemic circulation. The bioavailability of most polar or water-soluble drugs is not affected by age because they are not highly extracted by the liver. For many lipophilic drugs, this first pass through the liver is accompanied by pronounced (sometimes over 90%) extraction with only 5%-10% of the dose reaching the systemic circulation. It is clear that a small change in hepatic function may result in a large increase in bioavailability in those drugs which undergo a high presystemic first-pass metabolism (Montamat et al., 1989; Woodhouse, 1994). For example, decreased presystemic extraction in the elderly may lead to increases in the bioavailability of propranolol (Castleden and George, 1979) and nifedipine (Robertson et al., 1988), but usually not to a clinically significant extent. The changes may be more marked, however, in the frail and hospitalised elderly (Woodhouse, 1994).
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