Consumption of Charcoal‐Broiled Meat as an Experimental Tool for Discerning CYP1A2‐Mediated Drug Metabolism in vivo

Abstract

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.

CYP1A2, GSTM1, and GSTT1 Polymorphisms and Diet Effects on CYP1A2 Activity in a Crossover Feeding Trial

“…Although other studies have found that CYP1A2 * 1F has no effect on inducibility (47, 48), CYP1A2 * 1F has primarily been reported to alter inducibility, with C/Cs having lower inducibility than A/As (5, 49). We thus hypothesized that there would be no difference in CYP1A2 activity between genotypes on the basal diet, but those homozygous for CYP1A2 * 1F (C/C) would then have the lowest percent change in CYP1A2 activity in response to the inducing effect of cruciferous vegetables.…”

The Effect of Oral Contraceptives on the Pharmacokinetics of Melatonin in Healthy Subjects With CYP1A2 g.‐163C>A Polymorphism

“…Although the g.-163C>A polymorphism has been associated with higher enzyme inducibility by smoking, 28 this association has been controversial. 3,[29][30][31] For example, in pregnant women, the enhanced enzyme activity produced by smoking in carriers of the SNP g.-163C>A could not be detected. 5 Ghotbi and coworkers 32 found in their recent work that Koreans had a significantly lower CYP1A2 activity than Swedes, although they had the same CYP1A2 genotype, smoking habit, and OC use.…”

“…The CYP1A2 polymorphism did not cause significant changes in melatonin metabolism because the pharmacokinetic values of melatonin were about the same in non‐OC users of different genotypes and OC users of different genotypes. Although the g.‐163C>A polymorphism has been associated with higher enzyme inducibility by smoking, 28 this association has been controversial 3 , 29 – 31 . For example, in pregnant women, the enhanced enzyme activity produced by smoking in carriers of the SNP g.‐163C>A could not be detected 5 .…”

Bioaccessibility of polycyclic aromatic hydrocarbons: relevance to toxicity and carcinogenesis

“…The causative mechanism that underlie the increased clearance could be attributed to PAH induction of biotransformation enzymes, which are involved in the metabolism of these therapeutic agents [115]. The increased clearance of drugs in subjects exposed to PAHs may not be beneficial, resulting in larger doses, extended duration of treatment and hospital stay [116,117].…”