Evaluation of CYP2D6 oxidation of dextromethorphan and propafenone in a Chinese population with atrial fibrillation.
The objective of this study was to determine the percentage of patients with paroxysmal atrial fibrillation who were poor metabolizers of CYP2D6 in a Chinese population from Hong Kong and to assess the relationship between the dextromethorphan/dextrorphan ratio and the propafenone/5-hydroxypropafenone ratio or the steady-state propafenone concentration. Patients (n = 60) were recruited from the Arrhythmia Clinic at the University of Hong Kong and given dextromethorphan 30 mg. The dextromethorphan and dextrorphan concentrations in urine over the next 8 hours were used to determine metabolizer status. If the metabolic ratio was greater than 0.3, the patient was determined to be a poor metabolizer. In phase 2, patients (n = 38) were given propafenone 150 mg twice daily, and at steady state, the propafenone and 5-OH propafenone plasma concentrations were determined. It was found that 15% of the patients were poor metabolizers of dextromethorphan. There was a significant correlation between the metabolic ratios of dextromethorphan/dextrorphan and propafenone/5-OH propafenone (r = 0.49, p = 0.0019) and between the dextromethorphan/dextrorphan ratio and the concentration of propafenone (r = 0.32, p = 0.05). No correlations were found in the extensive or poor metabolizer subgroups. It was concluded that the percentage of poor metabolizers in atrial fibrillation patients from Hong Kong was much larger than in previous studies of Chinese patients who were not from Hong Kong. The ability to metabolize dextromethorphan to dextrorphan is related to the ability to metabolize propafenone to 5-hydroxypropafenone.
Chow
M S
MS
Department of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong.
White
C M
CM
Lau
C P
CP
Fan
C
C
Tang
M O
MO
D000889:Anti-Arrhythmia Agents / Q000097:blood*; D001281:Atrial Fibrillation / Q000097:blood / Q000201:enzymology* / Q000652:urine; D002681:China / Q000208:ethnology; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D003915:Dextromethorphan / Q000652:urine*; D003917:Dextrorphan / Q000652:urine; D018691:Excitatory Amino Acid Antagonists / Q000652:urine*; D005260:Female; D006723:Hong Kong; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011405:Propafenone / Q000031:analogs & derivatives* / Q000097:blood*
D000889:Anti-Arrhythmia Agents; D018691:Excitatory Amino Acid Antagonists; D003917:Dextrorphan; D011405:Propafenone; D003915:Dextromethorphan; C044307:5-hydroxypropafenone; D019389:Cytochrome P-450 CYP2D6