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The dependence of paracetamol absorption on the rate of gastric emptying.

Summary

1. The rate of gastric emptying was measured directly in 14 convalescent hospital patients and paracetamol absorption was studied following an oral dose of 15 g.

2. Rapid gastric emptying was associated with the early appearance of high peak plasma paracetamol concentrations whereas peak concentrations were low and occurred late when gastric emptying was slow.

3. There was a significant correlation between the rate of gastric emptying and the 0-4 and 0-24 h urinary excretion of paracetamol and its metabolites.

4. In five patients with abnormally slow gastric emptying the mean maximum plasma concentration and 0-4 and 0-24 h urinary excretion of paracetamol were significantly lower than in seven patients with normal gastric emptying rates while the time taken to reach maximum plasma concentrations was longer.

5. Individual differences in the rate of gastric emptying may contribute to variable absorption of many drugs.

There is often considerable individual variation in the rate at which orally administered drugs are absorbed in man. Physiological factors such as intestinal motility, the rate of gastric emptying, splanchnic blood flow and the volume, composition and pH of alimentary secretions are known to alter the rate of drug absorption in experimental animals, but their clinical significance is uncertain since few relevant studies have been carried out in man.

For a drug absorbed predominantly from the small intestine, the rate of gastric emptying will determine the time taken to reach the absorption site, and thus influence its rate of absorption. According to the pH-partition hypothesis, weakly basic lipid soluble drugs are absorbed much more rapidly from the small intestine than from the acid contents of the stomach (Brodie, 1964) and absorption should be

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