Consumption of charcoal-broiled meat as an experimental tool for discerning CYP1A2-mediated drug metabolism in vivo.
Cytochrome P450 1A2 (CYP1A2) is a major drug-metabolising enzyme. Polycyclic aromatic hydrocarbons, present in high concentrations in tobacco smoke and charcoal-broiled meat, are known to induce CYP1A2. The purpose of the present study was to validate enzyme induction by consumption of charcoal-broiled meat as an experimental tool for discerning CYP1A2-mediated drug metabolism in vivo. Twenty-four healthy, non-smoking men, all extensive metabolisers of sparteine (CYP2D6), participated in the study. All participants were genotyped for a putative CYP1A2-inducibility genotype. In the study diet period charcoal-broiled meat was served for lunch and dinner for five consecutive days. All participants were tested with probe reactions for CYP1A2 (caffeine) and CYP2C19 (proguanil) before and after consuming the study diet. Further, in three subgroups, they were tested with either the CYP1A2-substrate tacrine or probe reactions for CYP3A4 (quinidine) or CYP2C9 (tolbutamide). Neither probe reactions for CYP1A2, CYP2C9, CYP2C19 or CYP3A4 were affected by consumption of charcoal-broiled meat as practised in this study. No modifying role of the CYP1A2-inducibility genotype was evident. A number of experimental limitations are discussed, among them the lack of standardisation of exposure, the timing of phenotyping, and the choice of probe reactions. In conclusion, consumption of charcoal-broiled meat as practised in the present study appears not to be a useful experimental tool for discerning CYP1A2-mediated metabolism in vivo.
Larsen
John Teilmann
JT
Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. Teilmann@dadlnet.dk
Brøsen
Kim
K
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002606:Charcoal; D003296:Cooking; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004032:Diet; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008460:Meat; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011110:Polymorphism, Genetic; D002727:Proguanil / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013379:Substrate Specificity; D013619:Tacrine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D002606:Charcoal; D002110:Caffeine; D013619:Tacrine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002727:Proguanil