title: Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the "cocktail" approach.
abstract: Phenotyping for drug metabolizing enzymes and transporters is used to assess quantitatively the effect of an intervention (e.g., drug therapy, diet) or a condition (e.g., genetic polymorphism, disease) on their activity. Appropriate selection of test drug and metric is essential to obtain results applicable for other substrates of the respective enzyme/transporter. The following phenotyping metrics are recommended based on the level of validation and on practicability: CYP1A2, paraxanthine/caffeine in plasma 6 h after 150 mg caffeine; CYP2C9, tolbutamide plasma concentration 24 h after 125 mg tolbutamide; CYP2C19, urinary excretion of 4'-OH-mephenytoin 0-12 h after 50 mg mephenytoin; CYP2D6, urinary molar ratio debrisoquine/4-OH-debrisoquine 0-8 h after 10 mg debrisoquine; and CYP3A4, plasma clearance of midazolam after 2 mg midazolam (all drugs given orally).
authors.affiliation: Department of Pharmacology, Clinical Pharmacology Unit, University of Cologne, Cologne, Germany. uwe.fuhr@uk-koeln.de
authors.forename: U
authors.initials: U
authors.lastname: Fuhr
authors.forename: A
authors.initials: A
authors.lastname: Jetter
authors.forename: J
authors.initials: J
authors.lastname: Kirchheiner
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D002110:Caffeine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003647:Debrisoquin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010641:Phenotype; D013806:Theophylline / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014044:Tolbutamide / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D013806:Theophylline; C021183:1,7-dimethylxanthine; D003647:Debrisoquin