Chronic dog intestinal loop model for studying drug absorption as exemplified by beta-adrenoreceptor blocking agents, atenolol and propranolol

Abstract

Chronic in situ loops of dog small intestine (jejunum or ileum) were used to investigate the absorption of the beta-adrenoreceptor blocking agents atenolol and propranolol. Absorption measurements were made in conscious dogs by monitoring drug disappearance from solution in the loop, with correction for intestinal water absorption. The jejunum had a mean resting pH of 7.3 and a slight net secretion of water into the lumen; the ileum had a resting pH of 7.9 and a strong net absorption of water. Propranolol absorption was rapid and first order in both regions, with the ileum showing faster absorption than the jejunum due to its higher resting pH. In contrast, atenolol absorption was negligible in the jejunum and only moderate in the ileum. The data were quantitatively consistent with the pH-partition mechanism for the absorption of propranolol but not for atenolol. The model was validated for atenolol by showing that, following drug administration into jejunal and ileal loops, drug disappearance rates were similar to absorption rates calculated from systemic blood levels. This technique is useful, realistic, and relatively simple for studying intestinal drug absorption without seriously perturbing normal GI conditions.