title: Propafenone in a usual dose produces severe side-effects: the impact of genetically determined metabolic status on drug therapy.
abstract: We report the case of an elderly lady presenting with dizziness, a head injury resulting from a fall and bradycardia. Propafenone 150 mg t.i.d. had been prescribed for atrial fibrillation with tachyarrhythmia, induced by hyperthyroidism, 18 months earlier. A toxic concentration of parent propafenone, and no 5-hydroxy metabolite, was detected in a plasma sample. Symptoms disappeared after the discontinuation of propafenone. The poor metaboliser (PM) phenotype of sparteine/debrisoquine was assumed and subsequently confirmed by phenotyping (sparteine test) and genotyping (allele-specific polymerase chain reaction). The PM phenotype is common in European populations, with a prevalence of about 7%. If drugs with narrow therapeutic ranges undergo genetically polymorphic metabolism, toxicity may arise even with recommended doses. Individualization of doses is required to avoid adverse effects.
authors.affiliation: Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Mörike
authors.forename: S
authors.initials: S
authors.lastname: Magadum
authors.forename: T
authors.initials: T
authors.lastname: Mettang
authors.forename: E U
authors.initials: EU
authors.lastname: Griese
authors.forename: C
authors.initials: C
authors.lastname: Machleidt
authors.forename: U
authors.initials: U
authors.lastname: Kuhlmann
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011405:Propafenone / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D013034:Sparteine / Q000378:metabolism; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D013034:Sparteine; D011405:Propafenone; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin