ALTERED ABSORPTION OF DRUGS FROM THE RAT SMALL INTESTINE BY CARBONIC ANHYDRASE INHIBITION

¹ Department of Pharmacology and Toxicology, Purdue University, Lafayette, Indiana

The absorption of C¹⁴-dextroamphetamine sulfate, C¹⁴-salicylic acid and C¹⁴-urea from in vivo intestinal loops located either in the duodenum or ileum in male rats was determined after pretreatment with acetazolamide. In the ileum, after acetazolamide the absorption of d-amphetamine was decreased, that of salicylic acid was increased and that of urea was unchanged. The pH of the ileal contents was more acidic after acetazolamide. Plasma levels generally reflected the absorption of the respective compound. In the duodenum, after acetazolamide the absorption of d-amphetamine was increased, that of salicylic acid was decreased and that of urea was unchanged. The pH of the duodenal contents was not changed after acetazolamide. Again, plasma levels generally reflected the absorption of the respective compound. Tissue binding of each drug within the two intestinal tissues did not differ after acetazolamide. Carbonic anhydrase assays revealed that the acetazolamide treatment abolished enzyme activity in the intestinal tissue. The differential absorption pattern of the acidic and basic drug from duodenal and ileal sites suggests that the alterations in absorption were secondary physiologic changes resulting from carbonic anhydrase inhibition.