Effect of pH on theophylline transfer across the everted rat jejunum

The effect of pH on the cumulative transfer of theophylline across the everted rat jejunum in vitro was investigated. Intestinal integrity was assessed by light and scanning electron microscopy, while the biochemical viability of the intestine was evaluated using glucose transfer measurements. The initial (0-30 min) clearance of theophylline was directly proportional to the fraction un-ionized at pH 5.5, 7.4, 8.0, and 10.0. Plots of cumulative theophylline transfer versus time over 60 min were nonlinear, but could be subdivided into two linear segments of 30-min duration. Due to this nonlinearity, differences in theophylline transfer with pH were significant only over the first 30 min of the experiment. Intestinal tissue integrity and viability correlated with the time at which the clearance (slope) increased, while the magnitude of the increase in clearance was proportional to the degree of ionization of theophylline.