A quantitative review and meta-models of the variability and factors affecting oral drug absorption-Part II: gastrointestinal transit time

Abstract

This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) transit times of non-disintegrating single-unit ("tablet") and multiple-unit ("pellets/multi-unit tablet") solid dosage forms, characterize the effect of food on the values and variability in these parameters and present quantitative meta-models of the distributions of GI transit times in the respective GI regions to help inform models of oral drug absorption. 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. Meta-analysis used the "metafor" package of the R language. Meta-models of GI transit were assumed to be log-normally distributed between the studied populations. 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. Conversely, food caloric content reduced the variability but had no significant influence on the mean small intestinal transit time (SITT). Food had no significant effect on the transit time through the colon. The transit of pellets through the colon was significantly slower than that of single-unit tablets which is most likely related to their smaller size. GI transit times may influence the dissolution and absorption of oral drugs. The meta-models of GI transit times may 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.