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Cited by 108Drug Solubulity and Delivery SystemsAdvanced Drug Delivery SystemsPharmaceutical studies and practices

Impaired drug absorption due to high stomach pH: a review of strategies for mitigation of such effect to enable pharmaceutical product development

Mitra, Amitava, Kesisoglou, Filippos·2013·Molecular Pharmaceutics
DOI 10.1021/mp400256h
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Abstract

Published reports have clearly shown that weakly basic drugs which have low solubility at high pH could have impaired absorption in patients with high gastric pH thus leading to reduced and variable bioavailability. Since such reduction in exposure can lead to significant loss of efficacy, it is imperative to (1) understand the behavior of the compound as a function of stomach pH to inform of any risk of bioavailability loss in clinical studies and (2) develop a robust formulation which can provide adequate exposure in achlorhydric patients. In this review paper, we provide an overview of the factors that can cause high gastric pH in human, discuss clinical and preclinical pharmacokinetic data for weak bases under conditions of normal and high gastric pH, and give examples of formulation strategies to minimize or mitigate the reduced absorption of weakly basic drugs under high gastric pH conditions. It should be noted that the ability to overcome pH sensitivity issues is highly compound dependent and there are no obvious and general solutions to overcome such effect. Further, we discuss, along with several examples, the use of biopharmaceutical tools such as in vitro dissolution, absorption modeling, and gastric pH modified animal models to assess absorption risk of weak bases in high gastric pH and also the use of these tools to enable development of formulations to mitigate such effects.

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Crossref · 10.1021/mp400256h

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  • Development of formulations that can minimize or mitigate the effects of increased gastric pH on bioavailability is another way to solve the problem.

    “The other way is the development of “formulations that can minimize or mitigate the effects of increased gastric pH on the bioavailability” (117).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [117]

  • Coadministration of acidic beverages is one way of solving the problem of decreased bioavailability of drugs whose bioavailability is decreased under conditions of increased intragastric pH.

    “coadministration of acidic beverages is one way of solving the problem of decreased bioavailability of drugs whose bioavailability under conditions of increased intragastric pH (117).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [117]

  • There are a number of other drugs with decreased absorption at high intragastric pH, such as ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin, dipyridamole, raltegravir, alendronate, digoxin, and nifedipine.

    “there are a number of other drugs with decreased absorption at high intragastric pH, such as ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin, dipyridamole, raltegravir, alendronate, digoxin, and nifedipine, to name a few (117).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [117]

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Authors
Mitra, A., & Kesisoglou, F.
Affiliations
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author
Mitra, Amitava
ORCID
Venue
Molecular Pharmaceutics
Publisher
American Chemical Society (ACS)
Published
2013-07-22
Volume
10
Issue
11
Pages
3970-3979
ISSN
  • 1543-8384 (ISSN-L)
  • 1543-8392
DOI
10.1021/mp400256h
OpenAlex
W2010062367
Cited by
108
References
47
Citations by year
2026: 13 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 4 · 2014: 2 · 2013: 1
FWCI
0.54
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
weakly basic drugs, drug absorption, bioavailability, achlorhydria, formulation strategies, dissolution testing, absorption modeling, pharmacokinetics, pharmaceutical product development
MeSH terms
Absorption, Achlorhydria, Animals, Chemistry, Pharmaceutical, Dogs, Gastric Mucosa, Humans, Hydrogen-Ion Concentration, Famotidine

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