On the mechanism of intestinal absorption of drugs.

TLDR

Intestinal absorption is strongly influenced by pH, with acidic drugs absorbed less and basic drugs more as pH rises, and steady‑state concentration gradients favor bases in the lumen and acids in plasma, leading to rapid uptake of lipid‑soluble drugs and poor absorption of lipid‑insoluble ones. The study aims to test the hypothesis that the intestinal mucosa preferentially absorbs the unionized form of drugs. The authors attribute the observed concentration ratios to a slightly acidic environment at the intestinal‑blood barrier. The findings confirm that drug absorption correlates with the lipid‑water partition coefficient of the unionized form, supporting the view that gastrointestinal cell membranes are essentially lipidic.

Abstract

The intestinal absorption of acidic drugs is decreased severalfold and the absorption of basic drugs increased severalfold when the pH of the intestinal contents is raised from 4 to 8. This supports the hypothesis that the intestinal mucosa preferentially allows the absorption of the unionized form of a drug. Significant steady state concentration gradients of drugs are maintained between the gut lumen and plasma. Bases are concentrated within the gut lumen and acids are concentrated in plasma. These concentration ratios can be attributed to a slightly acidic environment at the intestinalblood barrier. There is a sufficient association between absorption of drugs and the lipid: water partition coefficients of their unionized moieties to justify the continued assumption that the gastrointestinal cell membranes are essentially lipoidal. Highly lipid-soluble drugs are in general rapidly absorbed while decidedly lipid-insoluble drugs are in general poorly absorbed.