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.

• Authors: Wei-Min Cai, Jun Xu, Bing Chen, Fu-Min Zhang, Yuan-Zhu Huang, Yin-Di Zhang
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 23 Issue 11 Pg. 1040-4 (Nov 2002) ISSN: 1671-4083 [Print] United States
• PMID: 12421483 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Propafenone
• Cytochrome P-450 CYP2D6

Topics

• Adult
• Aged
• Anti-Arrhythmia Agents (blood, pharmacology)
• Arrhythmias, Cardiac (blood)
• Cytochrome P-450 CYP2D6 (genetics, metabolism)
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Propafenone (blood, pharmacology)
• Ventricular Premature Complexes (blood, genetics)