Gastric and Intestinal Absorption of Captopril in Acutely and Chronically Treated Rats: Comparison with Salicylic Acid

Abstract

The gastric and intestinal absorption of captopril, an orally active angiotensin-converting enzyme inhibitor [antihypertensive agent] was determined using rat in situ gastric pouch and intestinal loop techniques and compared with the absorption of another acidic drug, salicyclic acid, whose absorption has been well established from both gastric and intestinal sites. Captopril absorption was determined at 2 initial intraluminal concentrations in acute (untreated) rats and in rats that had been treated with captopril. Salicyclic acid absorption was determined at 1 concentration in acute rats. During the 40-min experimental period, captopril absorption at the 4.6 mM dose from the gastric pouch was 17.0 .+-. 1.8% and 17.9 .+-. 5.4% in acute and chronically treated rats, respectively, and 33.6 .+-. 9.2% and 23.7 .+-. 7.6%, respectively, from the intestinal loop. At the 11.5 mM dose the captopril absorption in 40 min was 13.7 .+-. 2.7% and 17.3 .+-. 4.2% from the gastric pouch of acutely and chronically treated rats, respectively, and 17.8 .+-. 4.2% and 22.9 .+-. 3.3%, respectively, from the intestinal loop. As similar fractions of the different administered doses were absorbed from the respective gastric and intestinal sites in both acutely and chronically treated rats, the absorption process of captopril appears to be principally by passive diffusion and unaffected by chronic administration of captopril. In comparison salicylic acid was absorbed more rapidly and to a greater extent from both the gastric and intestinal preparations. The percent of salicyclic acid absorbed into the plasma at the 11.5 mM dose was 44.8 .+-. 4.4% and 65.3 .+-. 5.3% from the gastric and intestinal preparations, respectively. Gastric absorption of captopril evidently does occur, but its relative importance to intestinal absorption is dependent on the transit time from the gastric to intestinal site.