PH-DEPENDENCE OF RECTAL ABSORPTION OF THEOPHYLLINE FROM SOLUTIONS OF AMINOPHYLLINE INSITU IN RATS

The rectal absorption of theophylline was investigated in situ in rats as a function of luminal pH. As the pH near the membrane may deviate from the luminal pH by secretion, the neutralizing capacity of the rectum was determined by perfusing phosphate buffers with initial pH 5 or pH 9 for 2 h. The secretion of basic or acidic agents appeared to be strongly dependent on the deviation of the luminal pH from the physiological pH. In the first hour, respectively, 2.3 μmol of basic and 1.5 μmol of acidic agents per mg dry weight were produced, perfusing with pH 5 or pH 9 solutions. The secretion decreased when the pH of the perfusate approached physiological values, i.e. about pH 7.4. The influence of the composition of the perfusate on the absorption rate of theophylline (TP) from aminophylline (AP) solutions containing 10 mg TP/30 ml perfusate was studied. No difference in the absorption rate could be shown when phosphate buffers differing in strength and pH (between 5 and 10) were used. However, with solutions containing 50 mg TP and 130 mg TP per 30 ml, the absorption rates ofTP from isotonic phosphate buffers with pH 7, were higher than with pH 10, but far less than predicted by the pH-partition hypothesis (pKa theophylline = 8.4). The percentage of TP absorbed varied between 12.0 and 14.7% per 2 h for the pH 7 solutions and 8.2 and 12.4% per 2 h for the pH 10 solutions. The fractions absorbed at equal pH did not show a concentration dependency. Two explanations are proposed for the observed small pH dependency. Firstly, assuming that only TP molecules pass through the membrane, the absorption rate of TP is not dependent on the pH when a 'micro-climate' exists near the membrane with a pH not, or only slightly, dependent on the bulk pH. Because of the relatively large secretion of acidic agents by the mucosa during perfusion with basic solutions such a 'microclimate' is expected to exist. Secondly, TP ions might also be able to pass through the membrane as fast as TP molecules. © 1979.