Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/104876
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Type: Journal article
Title: A quantitative review and meta-models of the variability and factors affecting oral drug absorption-Part I: gastrointestinal pH
Author: Abuhelwa, A.
Foster, D.
Upton, R.
Citation: AAPS Journal, 2016; 18(5):1309-1321
Publisher: Springer
Issue Date: 2016
ISSN: 1550-7416
1550-7416
Statement of
Responsibility: 
Ahmad Y. Abuhelwa, David J. R. Foster and Richard N. Upton
Abstract: This study aimed 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 distributions of GI pH to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, GI pH under fed and fasted conditions. The GI tract was categorized into the following 10 distinct regions: stomach (proximal, mid-distal), duodenum (proximal, mid-distal), jejunum and ileum (proximal, mid, and distal small intestine), and colon (ascending, transverse, and descending colon). Meta-analysis used the "metafor" package of the R language. The time course of postprandial stomach pH was modeled using NONMEM. Food significantly influenced the estimated meta-mean stomach and duodenal pH but had no significant influence on small intestinal and colonic pH. The time course of postprandial 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. Colonic pH was significantly different for descending but not for ascending and transverse colon. Knowledge of GI pH is important for the formulation design of the pH-dependent dosage forms and in understanding the dissolution and absorption of orally administered drugs. The meta-models of GI pH may also be used as part of semi-physiological pharmacokinetic models to characterize the effect of GI pH on the in vivo drug release and pharmacokinetics.
Keywords: Fed state pH; gastric pH; gastrointestinal pH; meal caloric content; meta-analysis.
Rights: © 2016 American Association of Pharmaceutical Scientists
RMID: 0030063500
DOI: 10.1208/s12248-016-9952-8
Appears in Collections:Pharmacology publications

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