title: Case report: dose adjustment of warfarin using genetic information and plasma concentration monitoring.
abstract: OBJECTIVE
  Carbamazepine is known to interact with warfarin. We report on a case of this interaction and on its management using the patient's genetic information.
  
  
  METHODS
  The case concerns a 74-year-old Japanese woman with a mood disorder and a central retinal vein occlusion. She was on therapy that included carbamazepine and had started to take warfarin. However, the patient's prothrombin time expressed as the international normalized ratio (PT-INR) was 1·40 despite taking a dose three times higher than the average. The patient's S-warfarin concentration was 0·15 μg/mL and R-warfarin was 0·52 μg/mL. Her cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex, subunit 1 (VKORC1), genotypes were *1/*1 and -1639GA, respectively. The VKORC1 genotype indicated that she would require an even higher dose. We proposed a further increase in dose and the patient's PT-INR rose to 1·99.
  
  
  CONCLUSIONS
  The patient required a high warfarin dose because of the VKORC1 genotype, and induction of CYP2C9 by carbamazepine. We improved the patient's pharmacotherapy based on her genetic information.
authors.affiliation: Center for Pharmacy Practice, Faculty of Pharmacy, Keio University, Tokyo, Japan; Department of Pharmacy, Gunma University Hospital, Maebashi, Japan; Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Aomori
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Obayashi
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Kiyotani
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000494:pharmacology*; D065698:Cytochrome P-450 CYP2C9 Inducers / Q000494:pharmacology*; D004336:Drug Antagonism; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D010597:Pharmacogenetics; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D065698:Cytochrome P-450 CYP2C9 Inducers; D002220:Carbamazepine; D014859:Warfarin; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Japanese patient; carbamazepine; cytochrome P450 2C9; pharmacogenetics; pharmacy practice; therapeutic drug monitoring; vitamin K epoxide reductase complex, subunit 1; warfarin