TY - JOUR
T1 - Influence of CYP2D6 genotype on metoprolol plasma concentration and β-adrenergic inhibition during long-term treatment
T2 - A comparison with bisoprolol
AU - Nozawa, Takashi
AU - Taguchi, Masato
AU - Tahara, Katsutoshi
AU - Hashimoto, Yukiya
AU - Igarashi, Norio
AU - Nonomura, Makoto
AU - Kato, Bun Ichi
AU - Igawa, Akihiko
AU - Inoue, Hiroshi
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - Cytochrome P450 isozyme
KW - Gene polymorphism
KW - Isoproterenol
KW - β-adrenergic antagonist
UR - http://www.scopus.com/inward/record.url?scp=27344437084&partnerID=8YFLogxK
U2 - 10.1097/01.fjc.0000184117.76188.68
DO - 10.1097/01.fjc.0000184117.76188.68
M3 - 学術論文
C2 - 16220080
AN - SCOPUS:27344437084
SN - 0160-2446
VL - 46
SP - 713
EP - 720
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 5
ER -