| Drug absorption interactions between oral targeted anticancer agents and PPIs: is pH-dependent solubility the Achilles heel of targeted therapy? | |
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MedLine Citation:
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PMID: 22739140 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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). |
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Authors:
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N R Budha; A Frymoyer; G S Smelick; J Y Jin; M R Yago; M J Dresser; S N Holden; L Z Benet; J A Ware |
Publication Detail:
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Type: Journal Article; Review Date: 2012-06-27 |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: 92 ISSN: 1532-6535 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-24 Completed Date: 2012-10-18 Revised Date: 2013-02-15 |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 203-13 Citation Subset: AIM; IM |
Affiliation:
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Department of Clinical Pharmacology, Genentech, South San Francisco, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anticarcinogenic Agents
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pharmacokinetics,
therapeutic use* Drug Interactions Gastric Acid Gastric Acidity Determination Gastroesophageal Reflux / drug therapy*, metabolism Humans Hydrogen-Ion Concentration Intestinal Absorption Neoplasms / drug therapy*, metabolism Proton Pump Inhibitors / pharmacokinetics, therapeutic use* Solubility |
| Chemical | |
Reg. No./Substance:
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0/Anticarcinogenic Agents; 0/Proton Pump Inhibitors |
| Comments/Corrections | |
Comment In:
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Clin Pharmacol Ther. 2013 Feb;93(2):150
[PMID:
23169430
]
Clin Pharmacol Ther. 2013 Feb;93(2):151 [PMID: 23169432 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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