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A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption—Part I: Gastrointestinal pH

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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.

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Acknowledgments

A.Y.A is a PhD Candidate receiving an Endeavour Postgraduate Scholarship funded by the Department of Education and Training of the Australian Government (Scholarship ID no. 4088). The Australian Centre for Pharmacometrics is an initiative of the Australian Government as part of the National Collaborative Research Infrastructure Strategy.

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Authors and Affiliations

  1. Australian Centre for Pharmacometrics and Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia

    Ahmad Y. Abuhelwa, David J. R. Foster & Richard N. Upton

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  1. Ahmad Y. Abuhelwa
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  2. David J. R. Foster
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  3. Richard N. Upton
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Correspondence to Ahmad Y. Abuhelwa.

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Abuhelwa, A.Y., Foster, D.J.R. & Upton, R.N. A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption—Part I: Gastrointestinal pH. AAPS J 18, 1309–1321 (2016). https://doi.org/10.1208/s12248-016-9952-8

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