Interest and Limitations of Phenotype Determination of Hydroxylation Ability in Patients Treated with Propafenone

In order to confirm that variations in the plasma levels of propafenone in patients receiving the same daily dose are polyrnorphically distributed in relation to oxydative metabolism, the relationship between propafenone administration and debrisoquine metabolic phenotype was studied in two series of Caucasian patients with chronic supraventricular or ventricular arrhifthmias. In a first series of 16 Caucasian patients treated with propafenone, the poor metabolizer phenotype appeared to be more than 90%. In a second series of 13 Caucasian patients, two debrisoquine tests were performed: the first phenotype determination of debrisoquine hydroxylation ability was done without propafenone administration and the second determination when a steady state concentration of propafenone was reached. Of the 10 extensive metabolizers (determined without propafenone treatment), 7 patients became apparent poor metabolizers while considering the debrisoquine test during propafenone treatment with a general shift of the 13 studied patients to the upper values of log of the metabolic ratiodebrisoquine/4‐OH debrisoquine———‐suggesting deficiency in metabolizing debrisoquine. This study seems to indicate the presence of a common hydroxylation for propafenone and debrisoquine, which probably compete in the pathway. This metabolic competition should therefore be taken into consideration during phenotypic determination of hydroxylation ability.