Effect of pH, buffer concentration and buffer composition on the absorption of theophylline from the small intestine of the rat

The absorption of theophylline from the small intestine of the rat was investigated using buffer solutions of different pH (3.0–9.2), composition and concentration. The technique used, encloses luminal perfusion of an intestinal loop with collection of the blood draining the perfused loop, which enable calculation of absorption rates into the blood, disappearance rates from the lumen and mass balances. It was found, that in the presence of borate buffer, pH 9.2, the absorption rate of theophylline was decreased compared to the other perfusates. There was a significant difference between the absorption rate and the disappearance rate in the presence of phosphate and borate buffer. The low absorption rate in the presence of the borate buffer was attributed to a thickening effect of borate ions on intestinal mucus, thereby reducing the diffusion rate of theophylline. In another series of experiments, the absorption of caffeine was followed simultaneously and a Tris buffer was included to apply a pH of 9.2. In the presence of borate buffer, the absorption rate of both theophylline and caffeine was reduced compared to the other perfusates. In the presence of Tris buffers, there was a tendency to decreased absorption and disappearance rates for theophylline as wel as for caffeine. In the presence of phosphate and borate buffer, there was a difference between the absorption rate and the disappearance rate only for caffeine and not for theophylline. This was attributed to differences between the binding of caffeine and theophylline to intestinal mucus and/or tissue in the presence of phosphate and borate buffer. It was concluded, that buffers were not able to influence the pH at the membrane (microclimate pH). Furthermore, buffer components influenced the absorption process by affecting intestinal mucus and/or tissue. Thus, buffers should not be used in absorption studies