title: Comparative effects of the diastereoisomers, quinine and quinidine in producing phenocopy debrisoquine poor metabolisers (PMs) in healthy volunteers.
abstract: 1. A single oral dose (50 mg) of quinidine significantly increased the debrisoquine metabolic ratio in six healthy volunteers. For four of the volunteers the metabolic ratio changed to that typical of the poor metaboliser (PM) phenotype. 2. The effect of quinidine in producing debrisoquine oxidation "poor metaboliser" phenocopies persisted for at least 3 days but had disappeared by 1 week. 3. The debrisoquine metabolic ratios for the same six subjects were not significantly altered by the oral administration of quinine (200 or 400 mg), the diastereoisomer of quinidine. 4. The plasma pharmacokinetic parameters of both nortriptyline and desipramine in healthy volunteers were all changed to those more typical of the debrisoquine PM phenotype following the concomitant administration of quinidine (50 mg). 5. It is concluded that quinidine, but not its diastereoisomer quinine, is a potent selective inhibitor of the in vivo oxidation of debrisoquine and can produce an artifactual PM phenocopy in persons who are phenotypically extensive metaboliser (EM) phenotype status. The clinical implications of this observation are discussed.
authors.affiliation: Department of Pharmacology and Toxicology, St. Mary's Hospital Medical School, London, England.
authors.forename: R
authors.initials: R
authors.lastname: Ayesh
authors.forename: S
authors.initials: S
authors.lastname: Dawling
authors.forename: A
authors.initials: A
authors.lastname: Hayler
authors.forename: N S
authors.initials: NS
authors.lastname: Oates
authors.forename: S
authors.initials: S
authors.lastname: Cholerton
authors.forename: B
authors.initials: B
authors.lastname: Widdop
authors.forename: J R
authors.initials: JR
authors.lastname: Idle
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000328:Adult; D003647:Debrisoquin / Q000378:metabolism* / Q000652:urine; D003891:Desipramine / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D009661:Nortriptyline / Q000097:blood*; D010641:Phenotype; D011802:Quinidine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D012016:Reference Values; D013237:Stereoisomerism
chemical_list: D011803:Quinine; D009661:Nortriptyline; D011802:Quinidine; D003891:Desipramine; D003647:Debrisoquin