Adam Frymoyer

Publication Details

  • Drug Absorption Interactions Between Oral Targeted Anticancer Agents and PPIs: Is pH-Dependent Solubility the Achilles Heel of Targeted Therapy? CLINICAL PHARMACOLOGY & THERAPEUTICS Budha, N. R., Frymoyer, A., Smelick, G. S., Jin, J. Y., Yago, M. R., Dresser, M. J., Holden, S. N., Benet, L. Z., Ware, J. A. 2012; 92 (2): 203-213


    A majority of the novel orally administered, molecularly targeted anticancer therapies are weak bases that exhibit pH-dependent solubility, and suppression of gastric acidity with acid-reducing agents could impair their absorption. In addition, a majority of cancer patients frequently take acid-reducing agents to alleviate symptoms of gastroesophageal reflux disease, thereby raising the potential for a common but underappreciated drug-drug interaction (DDI) that could decrease the exposure of anticancer medication and result in subsequent failure of therapy. This article is a review of the available clinical literature describing the extent of the interaction between 15 orally administered, small-molecule targeted anticancer therapies and acid-reducing agents. The currently available clinical data suggest that the magnitude of this DDI is largest for compounds whose in vitro solubility varies over the pH range 1-4. This range represents the normal physiological gastric acidity (pH ~1) and gastric acidity while on an acid-reducing agent (pH ~4).

    View details for DOI 10.1038/clpt.2012.73

    View details for Web of Science ID 000306596300017

    View details for PubMedID 22739140

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