Effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia.
Abstract
AIM: To determine the effect of CYP2D6*10 genotype on propafenone
pharmacodynamics in Chinese patients with ventricular arrhythmia.
METHODS: Seventeen Chinese patients with ventricular premature contractions (VPC>
or =1000/d) were recruited. They were normal in routine laboratory testing and
administered propafenone hydrochloride 450-600 mg per day in three divided doses.
Twelve lead cardiogram and 24 h Holter monitoring were performed before and after
7 d treatment of propafenone. Steady-state peak and trough concentrations of
propafenone were measured by HPLC method. CYP2D6*10 genotypes of patients were
assayed by polymerase chain reaction (PCR) and restriction fragment length
polymorphism (RFLP).
RESULTS: Total inhibitory rate of VPC was 79.9 % in 17 patients with ventricular
arrhythmia after propafenone treatment. PR interval prolongation was increased
from 0.146 s+/-0.018 s to 0.161 s+/-0.022 s (P<0.05). CYP2D6 genotypes played an
important role in plasma levels and effects of propafenone. In 450 mg/d group,
patients with homozygous mutant of CYP2D6*10 not only had a Cmax of propafenone
two times as high as those of wild-type genotype, but also showed a two fold
higher inhibitory rate of VPC compared with those with homozygous CYP2D6*1
(P<0.05).
CONCLUSION: CYP2D6*10 genotype is relevant to decreased activity of CYP2D6 enzyme
in Chinese patients. Elevated plasma concentration is consistent with better
efficacy of propafenone in patients with ventricular arrhythmia.
Keywords:
pharmacodynamics in Chinese patients with ventricular arrhythmia.
METHODS: Seventeen Chinese patients with ventricular premature contractions (VPC>
or =1000/d) were recruited. They were normal in routine laboratory testing and
administered propafenone hydrochloride 450-600 mg per day in three divided doses.
Twelve lead cardiogram and 24 h Holter monitoring were performed before and after
7 d treatment of propafenone. Steady-state peak and trough concentrations of
propafenone were measured by HPLC method. CYP2D6*10 genotypes of patients were
assayed by polymerase chain reaction (PCR) and restriction fragment length
polymorphism (RFLP).
RESULTS: Total inhibitory rate of VPC was 79.9 % in 17 patients with ventricular
arrhythmia after propafenone treatment. PR interval prolongation was increased
from 0.146 s+/-0.018 s to 0.161 s+/-0.022 s (P<0.05). CYP2D6 genotypes played an
important role in plasma levels and effects of propafenone. In 450 mg/d group,
patients with homozygous mutant of CYP2D6*10 not only had a Cmax of propafenone
two times as high as those of wild-type genotype, but also showed a two fold
higher inhibitory rate of VPC compared with those with homozygous CYP2D6*1
(P<0.05).
CONCLUSION: CYP2D6*10 genotype is relevant to decreased activity of CYP2D6 enzyme
in Chinese patients. Elevated plasma concentration is consistent with better
efficacy of propafenone in patients with ventricular arrhythmia.