Abstract

Aim: The antiarrythmic drug propafenone is metabolized to its main metabolite by CYP2D6, suggesting that its metabolic ratio may be used for CYP2D6 phenotyping. However, reported ratios obtained from plasma concentrations did not reflect the phenotype. The objective of this paper 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 hydroxypropafenone were measured by HPLC. Results: The individual data for the respective propafenone/metabolite metabolic ratio in plasma samples taken at tmax 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 Cmax, i.e. 2 hours after drug intake).

Author Details

Authors

• E. Anzenbacherová¹
• P. Anzenbacher¹
• F. Perlík²
• J. Kvetina¹

Departments

• ¹ Institute of Experimental Biopharmaceutics, PRO.MED.CS Praha a.s. – Academy of Sciences Joint Institute, Hradec Králové, and
• ² Clinical Pharmacology Unit,
• ¹ st Department of Medicine, Faculty of Medicine, Charles University, Prague, Czech Republic

Address

Dr. E. Anzenbacherová; Institute of Experimental Biopharmaceutics, PRO.MED.CS Praha a.s. – Academy of Sciences Joint Institute, Heyrovského 1207, 50002 Hradec Králové, Czech Republic

Citation