Influence of CYP2C9 and vitamin k oxide reductase complex (VKORC)1 polymorphisms on time to determine the warfarin maintenance dose

Tohru Aomori, K. Obayashi, Y. Fujita, T. Araki, K. Nakamura, Tomonori Nakamura, M. Kurabayashi, Koujirou Yamamoto

Research output: Contribution to journalArticle

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Abstract

Polymorphisms in cytochrome P450 (CYP) 2C9 and the vitamin K oxide reductase complex subunit 1 (VKORC1) greatly affect the maintenance dose of warfarin. To prevent adverse events, immediate dose adjustment is required. The purpose of this study was to investigate the influence of these polymorphisms on the time taken to determine the warfarin maintenance dose for individual patients, and to assess the advantages of genotype-based dosing on initial anticoagulant therapy. We analyzed the genotypes of CYP2C9 and VKORC1 from 72 patients. The number of days taken to determine the maintenance dose was compared with the genotypes. The time taken to determine the maintenance dose of warfarin in group A (CYP2C9*1/*1, VKORC1 -1639AA), B (*1/*1, - 1639GA), C (*1/*3, - 1639AA), and D (*1/*3, - 1639GA) patients was 19±19, 28±28, 27±20 and 7 days, respectively. We analyzed the relationship between the initial dose of warfarin and the number of days required to determine the maintenance dose based on the VKORC1 genotypes. Patients with the VKORC1 - 1639AA genotype and who were initially treated with more than 3mg warfarin, required approximately 2 weeks for the maintenance dose to be determined. Patients with the VKORC1 - 1639GA genotype and the same initial warfarin dosage required approximately a month; however, patients initially treated with 5mg of warfarin only required 9.5±5.3 days. We found a tendency that the time taken to determine the warfarin maintenance dose depends on the genotypes. Genotype-based dosing may improve initial anticoagulant therapy.

Original languageEnglish
Pages (from-to)222-225
Number of pages4
JournalPharmazie
Volume66
Issue number3
DOIs
Publication statusPublished - 2011 Apr
Externally publishedYes

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Warfarin
NAD(P)H Dehydrogenase (Quinone)
Vitamins
Oxides
Oxidoreductases
Genotype
Anticoagulants
Cytochrome P-450 CYP2C9
Cytochrome P-450 Enzyme System
Therapeutics

ASJC Scopus subject areas

  • Pharmaceutical Science

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Influence of CYP2C9 and vitamin k oxide reductase complex (VKORC)1 polymorphisms on time to determine the warfarin maintenance dose. / Aomori, Tohru; Obayashi, K.; Fujita, Y.; Araki, T.; Nakamura, K.; Nakamura, Tomonori; Kurabayashi, M.; Yamamoto, Koujirou.

In: Pharmazie, Vol. 66, No. 3, 04.2011, p. 222-225.

Research output: Contribution to journalArticle

Aomori, Tohru ; Obayashi, K. ; Fujita, Y. ; Araki, T. ; Nakamura, K. ; Nakamura, Tomonori ; Kurabayashi, M. ; Yamamoto, Koujirou. / Influence of CYP2C9 and vitamin k oxide reductase complex (VKORC)1 polymorphisms on time to determine the warfarin maintenance dose. In: Pharmazie. 2011 ; Vol. 66, No. 3. pp. 222-225.
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