Quantitative Review and Meta-models of Gastrointestinal pH to Help Inform Mechanistic Oral Absorption Models

Aims: The oral bioavailability of drugs is influenced by a many factors including the regional gastrointestinal (GI) pH. Small changes in the GI pH profile may have a great influence on the dissolution and absorption of drugs that exhibit pH-dependent dissolution and absorption. The aims of this study were to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) pH in the different GI segments, characterize the effect of food on the values and variability in these parameters, and present quantitative meta-models of the distributions of GI pH to inform models of oral drug absorption.


Methods: The literature was systemically reviewed for the values of, and the variability in, GI pH under fed and fasted conditions in healthy subjects. The GI tract was categorised into 10 distinct regions: stomach (proximal, mid-distal), duodenum (bulb, mid-distal), jejunum & ileum (proximal jejunum, mid small intestine, and distal small intestine), and colon (ascending, transverse, and descending colon). Search engines of Web of Science, PubMed, and Google Scholar were used to screen for potential articles. The key words used in the search were "gastric pH", "small intestinal pH", "gastrointestinal pH", "colonic pH", AND "healthy subjects". References in primary articles of GI pH were reviewed and relevant studies were included in the analysis. Meta-analyses of the means and SDs of GI pH were conducted using the "metafor" package (1) of the R language. Modelling the time-course of postprandial stomach pH was performed in NONMEM (2). The effect of various categorical and continuous moderators on GI pH were investigated including method of pH measurement, study origin, caloric content of administered food, age, and time since last meal.


Results: The final number of studies included in the meta-analysis of GI pH was 23 with a total number of 89 mean and SD values for the pH in the different GI locations. The fed status was the only moderator that significantly affected the meta mean pH of the stomach (p-value < 0.001) but had no significant influence on small intestinal and colonic pH (Table I). The time-course of postprandial gastric pH was described using an exponential model. Increased meal caloric content increased the extent and duration of postprandial gastric pH buffering. The different parts of the small intestine had significantly different pH while colonic pH was not significantly different between ascending, transverse and descending colon. Meta-models of the respective GI region were presented based on the results of meta-analysis.


Conclusion: Knowledge of GI pH is important for the formulation of pH-dependent dosage forms and in understanding the dissolution and absorption of orally administered drugs. The meta-models of GI pH could be used as part of semi-physiological pharmacokinetic models to characterize the effect of GI pH on the in vivo drug release and pharmacokinetics.



1.     Viechtbauer W. metafor: Meta-Analysis Package for R. R package version. 2010;2010:1-0.

2.     Beal S, Sheiner LB, Boeckmann A, Bauer RJ. NONMEM User’s Guides, Part V. (1989-2009), Icon Development Solutions, Ellicott City, MD, USA. 2009. ADDIN EN.REFLIST