Rapid determination of CYP2D6 phenotype during propafenone therapy by analysing urinary excretion of propafenone glucuronides

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Abstract
Metabolism of the antiarrhythmic, propafenone, cosegregates with the sparteine/debrisoquine polymorphism. Patients devoid of CYP2D6 activity have a higher incidence of adverse effects than those with normal enzyme function. In this paper we present a method for rapid assignment of CYP2D6 phenotype using urinary excretion of intact glucuronides of propafenone (PPFG). After establishing an HPLC assay, urinary excretion of PPFG was quantified during one dosage interval and related to individual CYP2D6 activity as determined by phenotyping. We observed a close correlation of urinary excretion of PPFG with individual CYP2D6 activity (r=0.84, P<0.01) and conclude that this method is suitable for rapid assignment of phenotype during propafenone therapy.