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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Administration, Oral, Adult, Anti-Arrhythmia Agents, Area Under Curve, Asian Continental Ancestry Group, China, Cytochrome P-450 CYP2D6, Dextromethorphan, Excitatory Amino Acid Antagonists, Female, Fluoxetine, Half-Life, Humans, Isomerism, Male, Middle Aged, Phenotype, Propafenone, Reference Values, Serotonin Uptake Inhibitors.
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Does fluoxetine impair the CYP2D6-mediated metabolism of propafenone enantiomers in healthy Chinese volunteers? Context: To determine the effect of 20 mg/day fluoxetine on the pharmacokinetics of propafenone enantiomers and CYP2D6 activity by phenotyping with dextromethorphan. Nine healthy Chinese volunteers (seven men and two women) were included in a two-phase study. Dextromethorphan (20 mg) was given before and after subjects took 20 mg/day fluoxetine for 10 days, and the dextromethorphan metabolic ratio was calculated to determine CYP2D6 phenotype. Pharmacokinetic studies of propafenone enantiomers after a single oral 400 mg dose before and after pretreatment with 20 mg/day fluoxetine for 10 days were also conducted in these subjects. Reversed-phase HPLC with precolumn derivatization was used to determine enantiomeric concentrations of propafenone in plasma. Mean CYP2D6 dextromethorphan metabolic ratios before and after fluoxetine therapy were 0.028 +/- 0.031 and 0.080 +/- 0.058, respectively (P = .001), indicating that a strong inhibition of CYP2D6 by fluoxetine activity was observed in Chinese subjects. Propafenone metabolism was also impaired significantly after fluoxetine treatment. The elimination half-life, peak concentration, and area under the curve from 0 hours to infinity of two enantiomers after fluoxetine therapy were significantly increased compared with those at baseline (P < .01), whereas oral clearance decreased from 75.01 +/- 17.69 L/h to 49.36 +/- 8.62 L/h for S-propafenone (P = .005) and from 107.62 +/- 33.82 L/h to 70.60 +/- 12.42 L/h for R-propafenone (P = .027). In addition, fluoxetine increased the peak concentration of S-propafenone by 39% and that of R-propafenone by 71% (P < .05). A significant increase of the time to reach peak concentration was observed only in the R-enantiomer and not in the S-enantiomer of propafenone after fluoxetine therapy. There were no differences in the percentage changes of PR and QRS intervals before or after fluoxetine pretreatment at the time observed (P > .05).
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We conclude that fluoxetine may cause significant inhibition of the CYP2D6 activity as determined by dextromethorphan phenotyping. This inhibition impairs the metabolism of propafenone enantiomers in Chinese subjects. Caution must be exercised when fluoxetine and propafenone are coadministered to avoid potential toxicity. Final Decision: yes