Influence of CYP2D6 genotype on metoprolol plasma concentration and β-adrenergic inhibition during long-term treatment: A comparison with bisoprolol

Takashi Nozawa*, Masato Taguchi, Katsutoshi Tahara, Yukiya Hashimoto, Norio Igarashi, Makoto Nonomura, Bun Ichi Kato, Akihiko Igawa, Hiroshi Inoue

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

In patients routinely treated with metoprolol, influences of CYP2D6 genotype on the response of heart rate to isoproterenol (IP) were studied at its peak and trough concentrations and were compared with those of bisoprolol. In 72 patients treated with metoprolol or bisoprolol, CYP2D6 genotype (ie, CYP2D6*1, *2, *4, *5, *10, and *14) was determined. No patients except one who was heterozygous for CYP2D6*5 carried the null alleles of CYP2D6. The homozygote frequency for CYP2D6*10 was relatively high (19.4%) and these patients had greater peak and trough plasma concentrations of metoprolol than the other patients. Isoproterenol-induced percentage increases in heart rate were 58% and 38% less at the low and high rate of isoproterenol infusion (0.02 and 0.04 μg/kg/min), respectively, in patients homozygous for CYP2D6*10 than in the other patients at the trough, but not at the peak concentrations. In contrast, CYP2D6 genotype did not affect plasma concentrations of bisoprolol and the extent of its β-adrenergic inhibition. Thus, in patients routinely treated with metoprolol, CYP2D6 genotype significantly affects circadian variations of β-adrenergic inhibition induced by metoprolol. In contrast, bisoprolol has a relatively constant β-adrenergic inhibition independent of CYP2D6 genotype.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number5
DOIs
StatePublished - 2005/11

Keywords

  • Cytochrome P450 isozyme
  • Gene polymorphism
  • Isoproterenol
  • β-adrenergic antagonist

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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