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


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.


CONCLUSIONS
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).
Anzenbacherová
E
E
Institute of Experimental Biopharmaceutics, PRO.MED.CS Praha a.s.-Academy of Sciences Joint Institute, Hradec Králové, Czech Republic.
Anzenbacher
P
P
Perlik
F
F
Kvetina
J
J
D000328:Adult; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D011405:Propafenone / Q000493:pharmacokinetics*
D011405:Propafenone; D019389:Cytochrome P-450 CYP2D6