title: Identification of propafenone metaboliser phenotype from plasma and urine excretion data.
abstract: The aim of the study was to validate a test based on analyses of urine to identify the propafenone metaboliser phenotype during routine chronic therapy. Twenty seven patients chronically treated with propafenone were studied. A debrisoquine test was performed in 10. Propafenone and its metabolites in plasma and urine were measured by HPLC. Propafenone, 5-hydroxypropafenone and N-depropylpropafenone concentrations in plasma were 1.09, 0.182 and 0.101 ng.ml-1, respectively. Total recovery of the administered dose in urine was 30.7%. Two patients were identified as PM, based on the result of the debrisoquine test (log D/4OHD of 1.26 and 1.36). This finding was confirmed by the propafenone metabolic ratio in urine, but the plasma data did not permit clearcut separation of the phenotypes. Propafenone/5-hydroxypropafenone in plasma was not a good predictor of metabolizer phenotype. Although the number of patients who completed all three tests was limited, it is concluded that analysis of propafenone/5-hydroxypropafenone in urine collected between two consecutive doses at steady-state is more practical than the debrisoquine test and more specific than determining the propafenone/5-hydroxypropafenone ratio in plasma, for identification of the propafenone metaboliser phenotypes.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Latini
authors.forename: M
authors.initials: M
authors.lastname: Belloni
authors.forename: R
authors.initials: R
authors.lastname: Bernasconi
authors.forename: E
authors.initials: E
authors.lastname: Cappiello
authors.forename: P
authors.initials: P
authors.lastname: Giani
authors.forename: M
authors.initials: M
authors.lastname: Landolina
authors.forename: D
authors.initials: D
authors.lastname: Leopaldi
authors.forename: J M
authors.initials: JM
authors.lastname: Castel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002648:Child; D003647:Debrisoquin / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011405:Propafenone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D011405:Propafenone; C044307:5-hydroxypropafenone; D003647:Debrisoquin