抗不整脈薬の薬理遺伝学的情報に基づく効果的な治療薬物モニタリング  [in Japanese] Use of Pharmacogenetic Information for Therapeutic Drug Monitoring of an Antiarrhythmic Drug  [in Japanese]

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Author(s)

    • 土岐 浩介 Doki Kosuke
    • 筑波大学医学医療系臨床薬剤学 Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba

Abstract

 Antiarrhythmic drugs require therapeutic drug monitoring (TDM) to avoid adverse effects such as proarrhythmia. However, TDM is not necessarily used to adjust the dosage of antiarrhythmic drugs because there is a lack of information regarding the therapeutic range of the serum concentration and the selection of patients who require TDM. The aim of this review was to provide an overview of the pharmacogenetic information on the pharmacokinetics and drug response of flecainide, a class Ic antiarrhythmic drug with a sodium channel-blocking effect. A population pharmacokinetic analysis revealed that the <i>CYP2D6</i> genotype was a determining factor of the age-related decline in flecainide clearance. Elderly patients show large interindividual variability of flecainide clearance because they have a more pronounced effect of the <i>CYP2D6</i> genotype and require more frequent monitoring of serum flecainide concentrations. Carriers of an Asian-specific promoter haplotype B of the cardiac sodium channel gene (<i>SCN5A</i>) more frequently achieve clinically relevant flecainide efficacy even at lower concentrations. This suggests that the therapeutic range of serum flecainide concentrations is lower in <i>SCN5A</i> promoter haplotype B carriers than in the wild-type haplotype A homozygotes. The β1-adrenergic receptor Gly389 polymorphism decreases the antiarrhythmic efficacy of flecainide when co-administered with β-blockers. Carriers of Gly389 with co-administration of β-blockers may not achieve clinically relevant flecainide efficacy even when the serum flecainide concentrations are within the therapeutic range. These findings provide pharmacogenetic information for the effective utilization of TDM in antiarrhythmic drug therapy.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 138(9), 1145-1150, 2018

    Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130007474942
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • Article Type
    journal article
  • ISSN
    0031-6903
  • NDL Article ID
    029249913
  • NDL Call No.
    Z19-411
  • Data Source
    NDL  IR  J-STAGE 
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