Effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia.
OBJECTIVE
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).


CONCLUSIONS
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.
Cai
Wei-Min
WM
Department of Clinical Pharmacology, Jinling Hospital, Nanjing 210002, China. wmcai@public1.ptt.js.cn
Xu
Jun
J
Chen
Bing
B
Zhang
Fu-Min
FM
Huang
Yuan-Zhu
YZ
Zhang
Yin-Di
YD
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000097:blood*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011405:Propafenone / Q000097:blood* / Q000494:pharmacology; D018879:Ventricular Premature Complexes / Q000097:blood / Q000235:genetics
D000889:Anti-Arrhythmia Agents; D011405:Propafenone; D019389:Cytochrome P-450 CYP2D6