Document Detail


Drug absorption interactions between oral targeted anticancer agents and PPIs: is pH-dependent solubility the Achilles heel of targeted therapy?
MedLine Citation:
PMID:  22739140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
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:
Type:  Journal Article; Review     Date:  2012-06-27
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  92     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-24     Completed Date:  2012-10-18     Revised Date:  2013-02-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-13     Citation Subset:  AIM; IM    
Affiliation:
Department of Clinical Pharmacology, Genentech, South San Francisco, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Anticarcinogenic Agents / 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:
0/Anticarcinogenic Agents; 0/Proton Pump Inhibitors
Comments/Corrections
Comment In:
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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