title: The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: Deventer Hospital Thrombosis Center, Deventer, The Netherlands. beinemam@dz.nl
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Beinema
authors.forename: Petra H
authors.initials: PH
authors.lastname: de Jong
authors.forename: Har J M
authors.initials: HJ
authors.lastname: Salden
authors.forename: Merel
authors.initials: M
authors.lastname: van Wijnen
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
authors.forename: Jacobus R B J
authors.initials: JR
authors.lastname: Brouwers
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019338:Polypharmacy; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000074:Acenocoumarol