Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia: A 6-month follow-up study

H. Ngow, L. K. Teh, I. M. Langmia, W. L. Lee, R. Harun, R. Ismail, M. Z. Salleh

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of *1, *2, *3 and *4 CYP2C9 alleles, using a nested-allele-specific- multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9*1/*1 and 6.8% were CYP2C9*1/*3. Warfarin doses were higher in patients with CYP2C9*1/*1. Patients with the *1/*3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.

    Original languageEnglish
    Pages (from-to)641-651
    Number of pages11
    JournalXenobiotica
    Volume38
    Issue number6
    DOIs
    Publication statusPublished - Jun 2008

    Fingerprint

    Malaysia
    Warfarin
    Genotype
    Therapeutics
    Alleles
    Multiplex Polymerase Chain Reaction
    Polymerase chain reaction
    Informed Consent
    Medical Records
    Cytochrome P-450 CYP2C9
    Blood
    Retrospective Studies
    Observation
    Prospective Studies
    Hemorrhage
    DNA

    Keywords

    • CYP2C9
    • CYP2C9*1/*1
    • CYP2C9*1/*3
    • Ethnicity
    • Life-threatening bleeding
    • Malaysian pharmacodiagnostics
    • Warfarin

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Biochemistry
    • Pharmacology
    • Toxicology
    • Health, Toxicology and Mutagenesis

    Cite this

    Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia : A 6-month follow-up study. / Ngow, H.; Teh, L. K.; Langmia, I. M.; Lee, W. L.; Harun, R.; Ismail, R.; Salleh, M. Z.

    In: Xenobiotica, Vol. 38, No. 6, 06.2008, p. 641-651.

    Research output: Contribution to journalArticle

    Ngow, H. ; Teh, L. K. ; Langmia, I. M. ; Lee, W. L. ; Harun, R. ; Ismail, R. ; Salleh, M. Z. / Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia : A 6-month follow-up study. In: Xenobiotica. 2008 ; Vol. 38, No. 6. pp. 641-651.
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