The effect of E. coli STa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo

1. The effect of E. coli heat stable (STa) enterotoxin on the absorption of radio-labelled weak electrolytes and their appearance in peripheral blood was assessed in vivo by use of an intestinal recirculation procedure. 2. STa reduced the luminal disappearance (P less than 0.02) and peripheral blood appearance (P less than 0.02) of label from salicylic acid as well as the luminal disappearance (P less than 0.02) of diphenylhydantoin. 3. In contrast, STa increased the appearance in peripheral blood and disappearance from the lumen of label from morphine (P less than 0.05), amphetamine (P less than 0.01) and lignocaine (P less than 0.01). 4. Increased weak base (lignocaine) absorption can also be achieved by a combination of forskolin and theophylline which resembles STa in its ability to neutralise the usually acid surface pH of the proximal jejunum. 5. Increased weak base absorption and hindered weak acid absorption occurs despite a uniform reduction in net fluid absorption after STs exposure, making it unlikely that variations in fluid absorption account for the variations in drug absorption. 6. The ability of STa to elevate the mucosal surface pH (or acid microclimate) to neutral values, thereby altering the proportion of uncharged weak-electrolyte, may explain its different effects on weak acids and bases: neutralisation of the acid microclimate would increase the amount of undissociate weak base available for uptake.