Document Detail


The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery.
MedLine Citation:
PMID:  17397249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine the influence of NSAIDs on the international normalized ratio (INR) in patients with cytochrome P450 (CYP)-2C9 enzyme variants starting acenocoumarol (an oral coumarin) therapy during the first 7 days after total hip replacement surgery. METHODS: In this prospective study, an age-dependent protocol was used for the initiation of the acenocoumarol dose. Low-molecular-weight heparin was given for 5 days. The study included 100 patients undergoing total hip replacement surgery. After the inclusion of the last patient, polymerase chain reaction CYP2C9 mutation testing was performed for all patients. Drug-use evaluation of NSAIDs and other potential coumarin-drug interactions was also performed. RESULTS: Eleven patients had an INR on 1 or more days >4.9. There were 52 patients who were using NSAIDs. Patients with a CYP2C9 mutation had a mean INR curve similar to patients without the mutation when NSAIDs were not coadministered. Within the group of patients heterozygous for a CYP2C9 mutation (n=30) only concomitant use of a NSAID resulted in an INR >4.9 (0% vs 38.9%, p<0.05). CONCLUSION: In the group of patients with a CYP2C9 variant (*2 or *3 alleles), only concomitant use of a NSAID resulted in INRs >4.9. The cost effectiveness of CYP2C9 screening before elective surgery has yet to be determined.
Authors:
Maarten J Beinema; Petra H de Jong; Har J M Salden; Merel van Wijnen; Jan van der Meer; Jacobus R B J Brouwers
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Molecular diagnosis & therapy     Volume:  11     ISSN:  1177-1062     ISO Abbreviation:  -     Publication Date:  2007  
Date Detail:
Created Date:  2007-04-02     Completed Date:  2007-06-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101264260     Medline TA:  Mol Diagn Ther     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  123-8     Citation Subset:  IM    
Affiliation:
Deventer Hospital Thrombosis Center, Deventer, The Netherlands. beinemam@dz.nl
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MeSH Terms
Descriptor/Qualifier:
Acenocoumarol / administration & dosage,  adverse effects,  pharmacology*
Adult
Aged
Aged, 80 and over
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  adverse effects,  pharmacology*
Anticoagulants / administration & dosage
Arthroplasty, Replacement, Hip* / adverse effects
Aryl Hydrocarbon Hydroxylases / genetics*
Drug Interactions
Female
Humans
Male
Middle Aged
Polymorphism, Genetic*
Polypharmacy
Treatment Outcome
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Anticoagulants; 152-72-7/Acenocoumarol; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human

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


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