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Drug Absorption Interactions Between Oral Targeted Anticancer Agents and PPIs: Is pH‐Dependent Solubility the Achilles Heel of Targeted Therapy?
Author(s) -
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
Publication year - 2012
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2012.73
Subject(s) - drug , pharmacology , absorption (acoustics) , solubility , chemistry , medicine , cancer , drug interaction , organic chemistry , physics , acoustics
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). Clinical Pharmacology & Therapeutics (2012); 92 2, 203–213. doi: 10.1038/clpt.2012.73