Use of a propafenone metabolic ratio as a measure of CYP2D6 activity

Aim: The antiarrythmic drug propafenone is metabolized to its main metabolite by CYP2D6 phenotyping. However, reported ratios obtained from plasma did not reflect the phenotype. The objective of this was to find optimal conditions for plasma sampling based on pharmacokinetic data and to investigate whether propafenone/metabolite ratios reflect the CYP2D6 phenotype. Patients, materials and methods: The present study was conducted in 14 healthy volunteers phenotyped for CYP2D6 activity by a sparteine test. A single dose of oral propafenone (Profenorm PRO.MED.CS Praha a.s.) was administered, and venous blood samples were taken up to 24 hours thereafter. Propafenone and 24 hours thereafter. Propaferone and hydroxypropaferone were measured by HPLC. Results: The individual data for the respective propafenone/metabolite metabolic ratio in plasma samples taken at t(max) correlated well with the sparteine metabolic ratio used routinely for CYP2D6 phenotyping. However, when the samples were taken 4 hours after drug intake, the correlation was poor. Conclusion: The results indicate a possibility to use the propafenone metabolic ratio for determination of the CYP2D6 phenotype in plasma samples taken at single time point (close to the Cmas. i.e. 2 hours after drug intake).