Document Detail


Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting.
MedLine Citation:
PMID:  16192915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Postoperative nausea and vomiting (PONV) affects approximately one third of patients and may lead to aspiration, dehiscence, esophageal rupture, and increased treatment costs if inadequately controlled. An important therapeutic option for prevention of PONV is 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists. Nonetheless, therapeutic failure sometimes occurs. Metabolism by the cytochrome P450 (CYP) system differs among the 5-HT3 receptor antagonists, and provides a rational explanation for decreased therapeutic efficacy in some patients. Four of the 5-HT3 receptor antagonist agents (dolasetron, ondansetron, palonosetron, and tropisetron) are metabolized in various degrees via CYP2D6, an isoform subject to marked genetic polymorphism. In patients with duplicate CYP2D6 alleles, degradation into inactive metabolites occurs rapidly with these four 5-HT3 receptor antagonists, resulting in decreased efficacy for preventing PONV. Granisetron is the only agent in this class that is not metabolized via CYP2D6. Instead, granisetron is metabolized via the CYP3A4 isoform, which is not subject to significant genetic polymorphism. CYP2D6 genotype screening prior to PONV treatment may allow for modification of antiemetic dosing. An alternative is to use a 5-HT3 agent that is metabolized independently of the CYP2D6 isoform, such as granisetron, that would obviate the need for genotyping and may lead to improved prophylaxis of PONV.
Authors:
Piotr K Janicki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2005-09-26
Journal Detail:
Title:  Medical science monitor : international medical journal of experimental and clinical research     Volume:  11     ISSN:  1234-1010     ISO Abbreviation:  Med. Sci. Monit.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-29     Completed Date:  2006-01-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9609063     Medline TA:  Med Sci Monit     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  RA322-8     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA. pjanicki@psu.edu
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MeSH Terms
Descriptor/Qualifier:
Cytochrome P-450 CYP2D6 / genetics,  metabolism*
Cytochrome P-450 Enzyme System / metabolism
Genotype
Humans
Postoperative Nausea and Vomiting / enzymology,  prevention & control*
Receptors, Serotonin, 5-HT3 / antagonists & inhibitors*
Serotonin Antagonists / therapeutic use*
Chemical
Reg. No./Substance:
0/Receptors, Serotonin, 5-HT3; 0/Serotonin Antagonists; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Cytochrome P-450 CYP2D6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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