ABSORPTION OF DRUGS FROM THE RAT SMALL INTESTINE

TLDR

Drug absorption rates were measured by perfusing drug solutions through the entire small intestine of anesthetized rats. Drug absorption is best explained by simple diffusion of the unionized drug across a likely lipophilic barrier. Rapid absorption occurs for drugs whose ionization favors the unionized form (acidic drugs with pKa > 3 and basic drugs with pKa < 8), while stronger acids and bases are absorbed slowly or not at all, and continuous perfusion distinguishes rapid, moderate, and very slow absorption.

Abstract

The relative rates of absorption of a large number of drugs have been measured by perfusing solutions of drugs through the entire small intestine of the anesthetized rat. A single perfusion of the small intestine differentiated very rapid absorption from less rapid absorption. A continuous recirculation of the drug solution through the intestine separated less rapid absorption from very slow absorption. The degree of ionization of an organic electrolyte in solution appears to be one of the most important factors determining its absorption from the rat small intestine. Acidic drugs were rapidly absorbed if their pK a 9s were greater than 3. Basic drugs were rapidly absorbed if their pK a 9s were less than 8. The stronger acids and bases were relatively slowly absorbed and the absorption of very strong acids and bases was imperceptible. Absorption of drugs from the rat small intestine can be best explained by assuming simple diffusion of unionized drug across a barrier which may be lipoidal in nature.