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- Title
Drug Absorption Interactions Between Oral Targeted Anticancer Agents and PPIs: Is pH-Dependent Solubility the Achilles Heel of Targeted Therapy?
- Authors
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
- Abstract
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).
- Subjects
DRUG absorption; ANTINEOPLASTIC agents; DRUG interactions; PROTON pump inhibitors; GASTRIC acid; PH effect; GASTROESOPHAGEAL reflux
- Publication
Clinical Pharmacology & Therapeutics, 2012, Vol 92, Issue 2, p203
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2012.73