The influence of pH on rectal absorption of sodium benzoate studied in man by rectal lumen perfusion

• Published in: Journal of pharmacokinetics and biopharmaceutics Vol. 18; no. 1; p. 1
• Main Authors: Böttger, W M, Schoonen, A J, de Vries-Nijboer, G W, Visser, J, Meijer, D F
• Format: Journal Article
• Language: English
• Published: United States 01.02.1990
• Subjects: Benzoates - pharmacokinetics; Benzoic Acid; Buffers; Cell Membrane - metabolism; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Octanols; Perfusion; Rectum - metabolism; Solubility; Water
• ISSN: 0090-466X
• DOI: 10.1007/BF01063619

The influence of pH on rectal absorption of sodium benzoate in man was studied by means of a rectal lumen perfusion method and compared with in vitro measurements on diffusional transport of sodium benzoate across an octanol/water interface. For nonbuffered solutions of benzoate in vitro, it was shown that mass flux across an octanol/water interface occurs in agreement with the pH-partition model. In vivo however, mass flux increases less with decreasing pH of unbuffered perfusate than is anticipated on the basis of the pH-partition model. Probably an alkaline flow across the rectal mucosa into the lumen is present as a physiological neutralization mechanism. In contrast, buffered solutions of benzoate show a linear relationship between mass flux and decreasing pH in vitro as well as in vivo. The effect of buffer on the concentration profile of benzoic acid is qualitatively explained. It is shown that an alkaline flow across the rectal mucosa only slightly influences absorption of benzoic acid from strongly buffered solutions in the rectal lumen. It is concluded that the use of strong buffers in rectal solutions induces a drastic effect on the pH of the boundary layer, an effect not seen for unbuffered solutions. This phenomenon does not invalidate the pH-partition hypothesis but can be explained by it.