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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 S3: Variant alleles frequencies (%).
Isoforms and variant allele Percentage of study population (n)
Predicted phenotype
CYP2B6
*1/*1
*1/*5
83.3 (25) 16.7 (5)
NM NM CYP2C9
*1/*1
*1/*2
*1/*3
*2/*2
56.7 (17) 23.3 (7) 6.7 (2) 10 (3)
NM IM IM PM CYP2C19
*1/*1
*1/*2
*1/*4
*1/*17
*2/*17
*17/*17
50 (15) 13.3 (4) 3.3 (1) 20 (6) 6.7 (2) 3.3 (1)
NM IM IM RM IM UM CYP2D6
*1/*1
*1/*2
*1/*4
*1/*10
*1/*41
*2/*2
*2/*4
*2/*41
*4/*4
*4/*12
*6/*12
*10/*41
13.3 (4) 13.3 (4) 13.3 (4) 6.7 (2) 3.3 (1) 3.3 (1) 16.7 (5) 10 (3) 3.3 (1) 3.3 (1) 3.3 (1) 3.3 (1)
NM (AS = 2) NM (AS = 2) IM (AS = 1) NM (AS = 1.25) NM (AS = 1.25) NM (AS = 2) IM (AS = 1) NM (AS = 1.5) PM (AS = 0) PM (AS = 0) PM (AS = 0) IM (AS = 0.75) AS = activity score, IM = intermediate metabolizer, NM = normal metabolizer, PM = poor metabolizer, RM = rapid metabolizer, UM = ultra-rapid metabolizer.
