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Impact of acute inflammation on cytochromes P450 activity assessed by the Geneva Cocktail
LENOIR, Camille, et al.
Abstract
Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation down-regulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in thirty patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) post-surgery and at discharge.
Capillary blood samples were collected 2h after cocktail intake to assess metabolic ratios (MR). Serum inflammatory markers (CRP, IL-6, IL-1β, TNF-α, IFN-γ) were also measured in blood. CYP1A2 MR decreased by 53% (p
LENOIR, Camille, et al . Impact of acute inflammation on cytochromes P450 activity assessed by the Geneva Cocktail. Clinical Pharmacology and Therapeutics , 2020
PMID : 33341941 DOI : 10.1002/cpt.2146
Available at:
http://archive-ouverte.unige.ch/unige:149068
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Table S1: SNP polymorphisms of CYP2B6, 2C9, 2C19 and 2D6 assessed in the study.
Gene rs number
CYP2B6 rs28399499
rs34223104 rs3211371
CYP2C9 rs28371685
rs1799853 rs1057910 rs56165452 rs28371686 hCV32287221
CYP2C19 rs6413438
rs12248560 rs4244285 rs4986893 rs28399504 rs56337013 rs72552267 rs72558186 rs41291556 rs17884712
CYP2D6 rs16947
rs1135840 rs5030862 rs5030865 rs28371706 rs59421388 rs35742686 rs1065852 rs28371725 rs3892097 rs5030655 rs5030867 rs5030865 hCV32407229
