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

Aims: The in vivo performance of single-unit ("tablet/capsule") and multiple-units ("pellets, multi-tablets") dosage forms may sometime be markedly influenced by their transits through the gastrointestinal tract (1). The aims of this study were to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) transit times of single-unit and multiple-units solid dosage forms, characterize the effect of food on the values and variability in these parameters, and to present quantitative meta-models of the distributions of GI transit times in the respective GI regions to help inform models of oral drug absorption.

 

Methods: The literature was systemically reviewed for the values of, and the variability in, gastric, small intestinal, and colonic transit times under fed and fasted conditions in healthy subjects. Search engines of Web of Science, PubMed, and Google Scholar were used to screen for potential articles. The key words used for search were "gastric emptying", "small intestinal transit", "colonic transit", AND "non-disintegrating tablets" OR "pellets", AND "healthy subjects". References located in primary articles of GI transit times were reviewed and relevant studies were included in the analysis. Meta-analyses of the means and SDs of GI transit times were conducted using the "metafor" package (2) of the R language. Meta-models of GI transit were assumed to be log-normally distributed between the studied populations.

 

Results: Twenty nine studies including 125 reported means and standard deviations were used in the meta-analysis. Caloric content of administered food increased variability and delayed the gastric transit of both pellets and tablets (Table I). Small intestinal transit time (SITT) was significantly enhanced with increased food caloric content. The variability in the SITT of pellets was higher than tablets, regardless of the fed status. Food had no significant effect on the transit time through the colon; however, less is known about the transit of dosage forms through colon.

 

Conclusion: GI transit times may influence the dissolution and absorption of orally administered drugs. The meta-values of GI transit times could be used as part of semi-physiological absorption models to characterize the influence of transit time on the dissolution, absorption and in vivo pharmacokinetic profiles of oral drugs.

 

References:

1. Connor A. Location, location, location: gastrointestinal delivery site and its impact on absorption. Therapeutic delivery. 2012;3(5):575.

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