The effect of E. coli STa enterotoxin on the absorption of weakly dissociable anti‐malarial drugs from rat intestine in vivo

Abstract

The effect of E. coli heat stable (STa) enterotoxin on the absorption of radiolabelled anti‐malarial weak bases and their appearance in peripheral blood was assessed in vivo by a recirculation procedure in rat intestinal loops. Enterotoxin increased the jejunal disappearance of quinine (P < 0.05), trimethoprim (P < 0.05), proguanil (P < 0.05) and chloroquine (P < 0.001) and left pyrimethamine disappearance unaltered. Peripheral blood levels of trimethoprim (P < 0.02) and proguanil (P < 0.05) were higher after STa exposure. In the ileum, enterotoxin increased the luminal disappearance (P < 0.05) and peripheral blood appearance (P < 0.001) of chloroquine. The luminal disappearance rate of trimethoprim was reduced (P < 0.05) and that of pyrimethamine unchanged. The increased jejunal absorption of the anti‐malarial drugs occurred despite STa causing a reduction in the amount of net fluid absorption. It seems likely that the enhanced absorption with STa exposure is related to the effect of STa on the microclimate pH. An elevation in the microclimate pH would increase the amount of undissociated weak base available for non‐ionic diffusion. The favourable elevation of microclimate pH by STa seemed to be outweighed by the reduced fluid absorption in the ileum. Only chloroquine still showed enhanced absorption in the ileum and this may have been because unlike the other antimalarial drugs, chloroquine has two dissociable groups likely to be affected by the mucosal surface pH changes.