AI Article Synopsis
- The study aimed to understand how CYP1A2 enzyme activity varies with factors like smoking, gender, age, and genetic polymorphisms.
- Results showed that smoking significantly increases CYP1A2 activity, with men generally having higher activity levels and age-related differences noted only in nonsmoking women.
- The -163C>A polymorphism affected CYP1A2 activity in smokers, and the H4 haplotype also had significant relevance, indicating genetic factors play a role, but smoking was the strongest influence overall.
Article Abstract
Aims: To study the variation in CYP1A2 activity in relation to smoking, gender, age and CYP1A2 polymorphisms.
Materials & Methods: CYP1A2 activity was determined by plasma paraxanthine:caffeine ratio (17X:137X) 4 h after the intake of a standardized cup of coffee in 146 Turkish healthy volunteers. Seven CYP1A2 polymorphisms (-3860G>A, -3113G>A, -2467del/T, -739T>G, -729C>T, -163C>A and 5347T>C) were analyzed.
Results: The 17X:137X ratios were increased in smokers (p < 0.0001) and tended to be higher in men both among nonsmokers (p = 0.051) and smokers (p = 0.064). Age-related differences were observed only among nonsmoking women (p = 0.024). The -163C>A polymorphism correlated with 17X:137X ratios only in smokers (p = 0.006). Furthermore, increased 17X:137X ratios were observed in CYP1A2 haplotype H4 (-3860G, -3113G, -2467del, -739T, -729C, -163A and 5347T) carriers in the overall study population (p = 0.026). Multiple regression analyses including smoking, gender, -163C>A genotype and age revealed a significant influence of smoking (p < 0.0001) and gender (p = 0.002) in the overall study population. However, in nonsmokers only the influence of gender remained significant (p = 0.021), while in smokers the influence of the -163C>A genotype held the statistical significance (p = 0.019). The influence of haplotype H4 remained significant (p = 0.028) in the overall study population in similar analyses.
Conclusion: Smoking has the strongest impact on CYP1A2 activity, while gender and haplotype H4 showed marginal effects. The influence of the -163C>A polymorphism on CYP1A2 activity in smokers suggests an effect on the inducibility of the enzyme.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2217/pgs.09.22 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Construction of a CYP2J2-Template System and Its Application for Ligand Metabolism Prediction.
Food Saf (Tokyo)
December 2024
Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
A Template system for the understanding of human CYP2J2-mediated reactions was constructed from the assembly of the ligands with the introduction of ideas of allowable width, Trigger-residue and the residue-initiated movement of ligands in the active site, which were in common with other Template* systems for human CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP3A4, CYP3A5, and CYP3A7 (Drug Metab Pharmacokinet 2016, 2017, 2019, 2020, 2021, 2022, 2023, 2024, and in press 2024). CYP2J2 system also includes ideas of bi-molecule binding of ligands on the Template. From their placements on the Template and rules for interaction modes, verifications of good and poor substrates, regio/stereo-selectivity, and inhibitory interaction became available faithfully for these ligands.
View Article and Find Full Text PDFEvaluation of the Effect of Risankizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients with Moderately to Severely Active Ulcerative Colitis or Crohn's Disease.
Clin Pharmacokinet
December 2024
Clinical Pharmacology, AbbVie Inc., Dept R4PK, Bldg AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064-1802, USA.
Background And Objective: The objective of this study was to characterize the effects of risankizumab on the pharmacokinetics of cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A substrates in patients with moderately to severely active Crohn's disease (CD) or ulcerative colitis (UC) using a cocktail approach.
Methods: Patients with CD or UC (n = 20) received single doses of probe substrates for CYP1A2 (caffeine 100 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), CYP2D6 (metoprolol 50 mg), and CYP3A (midazolam 2 mg) before and after intravenous infusions of risankizumab 1800 mg once every 4 weeks for four doses. Serial blood samples were collected for determination of concentrations of the CYP probe drugs and metabolites with and without risankizumab.
In Vitro and In Silico Biological Activities Investigation of Ethyl Acetate Extract of Schott Leaves Collected in Algeria.
Plants (Basel)
December 2024
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
This investigation aimed to assess the in vitro and in silico biological properties of the ethyl acetate (EtOAc) extract obtained from leaves of Schott collected in Algeria. The phytochemical screening data disclosed that flavonoids, tannins, coumarins, saponins, and anthocyanins were abundant. High levels of total phenolics, total flavonoids and flavonols (523.
View Article and Find Full Text PDFHuman Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms: A Review.
Cells
November 2024
Independent Researcher, 108815 Moscow, Russia.
Background: Cytochromes P450 (CYPs) are heme-containing oxidoreductase enzymes with mono-oxygenase activity. Human CYPs catalyze the oxidation of a great variety of chemicals, including xenobiotics, steroid hormones, vitamins, bile acids, procarcinogens, and drugs.
Findings: In our review article, we discuss recent data evidencing that the same CYP isoform can be involved in both bioactivation and detoxification reactions and convert the same substrate to different products.
Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).
Cancer Chemother Pharmacol
December 2024
Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Background: The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.
Methods: We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!