Biotransformation pathways and the potential for drug-drug interactions of the orally active antifungal terbinafine were characterized using human liver microsomes and recombinant human cytochrome P-450s (CYPs). The terbinafine metabolites represented four major pathways: 1) N-demethylation, 2) deamination, 3) alkyl side chain oxidation, and 4) dihydrodiol formation. Michaelis-Menten kinetics f...

Phenacetin is widely used as an in vitro probe to measure CYP1A2 activity across species. To investigate whether phenacetin can be used as an in vivo probe substrate to phenotype CYP1A2 activity in dogs, beagle dogs previously genotyped for a single nucleotide polymorphism that yields an inactive CYP1A2 protein were selected and placed into one of three groups: CC (wild-type), CT (heterozygous)...

The ageing process is influenced by many internal and external factors. The toxic substances in the environment can cause genomic damages to cells, which increase the risk of early ageing. Furthermore, the cytochrome P450 1A2 (CYP1A2) gene polymorphism is a susceptibility factor and may enhance the risk of DNA damage in cells. The current study was carried out to show whether occupational expos...

The in vitro N-hydroxylation of guanabenz as well as the corresponding N-dehydroxylation of guanoxabenz has been previously detected in biotransformation studies with microsomal fractions of different species including human hepatic microsomes. Furthermore, the N-hydroxylation of guanabenz was found to be catalyzed by enriched cytochrome P450 (P450) fractions in reconstituted systems. Strong co...

The article by Miyata et al. (2003) in the April issue of Drug Metabolism and Disposition reported that thalidomide inhibited the proliferation of embryo fibroblasts in the presence of microsomes from rabbit liver or HepG2 cells pretreated with 3-methylchlolanthrene (3-MC). Mouse liver microsomes or microsomes from human HepG2 cells pretreated with vehicle did not cause inhibition. The inhibiti...

The CYP1A P450 subfamily consists of two members, CYP1A1 and CYP1A2 in mouse, rat, dog, monkey and human. CYP1A shows a quite strong conservation among species with an identity to human higher that 80% in rat (83 and 80%, respectively for CYP1A1 and CYP1A2), mouse (83 and 80%, respectively for CYP1A1 and CYP1A2), dog (84% for CYP1A2) and monkey (95% for both CYP1A1 and CYP1A2). Drug-drug intera...

Procarcinogen-activating cytochrome P450 (CYP) enzymes such as CYP1B1, CYP1A1, and CYP1A2 are considered to play an important role in chemical carcinogenesis. However, conflicting data exist with respect to CYP1B1 expression in human liver. In the present study, we measured CYP1B1 mRNA and protein expression in liver samples from 12 individuals (7 nonsmokers, 4 smokers, and 1 ex-smoker) and com...

with obstructive airway diseases. It is well known that theophylline has a narrow therapeutic range being a plasma concentration of 10—20 mg/ml and is extensively metabolized in humans. Many articles have been published on the drug interactions of theophylline with other coadministered drugs mediated by cytochrome P450 (CYP) 1A2, which is the major metabolizing enzyme for theophylline. For exam...

Phenacetin is widely used as an in vitro probe to measure CYP1A2 activity across species. To investigate whether phenacetin can be used as an in vivo probe substrate to phenotype CYP1A2 activity in dogs, beagle dogs previously genotyped for a single nucleotide polymorphism that yields an inactive CYP1A2 protein were selected and placed into one of three groups: CC (wild-type), CT (heterozygous)...

The aim of this meta-analysis was to assess the association between a polymorphism (-3860 G > A) in the cytochrome P450 1A2 (CYP1A2) gene and lung cancer susceptibility. Relevant studies were retrieved from the PubMed and EMBase databases, and additionally evaluated for conformance with the inclusion criteria. The odds ratios (ORs) and their 95% confidence intervals (95%CIs) in all selected stu...